Start 196,524 GroupStart 196,524 Chromosome Y 1,735 Mitochondrial 1 Non-polymorphic (all samples) 12,715 Low cluster separation (< 0.4) 12,510 Low call frequency(< 0.98) 2,243

Sample QC

Start lt99 Fail Autosomal

Fail IBD

Fail PCA Remaining

ACPA-POS

ACPA-NEG

Call

frequency Heterozygosity

UK cases 4269 243 5 126 25 3870 2406 1000

UK controls 8926 145 5 285 61 8430 - -

Swedish EIRA cases 2968 62 14 41 89 2762 1762 987

Swedish EIRA controls 2106 76 6 22 62 1940 - -

US cases 3621 487 19 488 91 2536 1803 593

US controls 3887 480 41 98 1134 2134 - -

Dutch cases 704 12 3 16 25 648 330 301

Dutch controls 2085 23 1 33 24 2004 - -

Swedish Umea cases 1085 139 2 85 7 852 524 242

Swedish Umea controls 1021 3 3 44 8 963 - -

Spanish cases 914 53 10 13 31 807 397 216

Spanish controls 447 14 2 29 3 399 - -

Total cases 13561 996 53 769 268 11475 7222 3339

Total controls 18472 741 58 511 1292 15870

Supplementary Table 1 Quality control measures implemented on the Immunochip array data illustrating numbers of samples failing in each collection

Nature Genetics doi101038ng2369

Start 196524

Chromosome Y 1735

Mitochondrial 1

Non-polymorphic (all samples) 12715

Low cluster separation (lt 04) 12510

Low call frequency(lt 098) 2243

Illumina default exclusions 936

Duplicate SNPs 835

Remaining for analysis 165549

Group

SNP loss

Final Call Frequency

(lt099) HWE MAF

UK 2468 680 36543 125858

US 10484 299 34769 119997

SE-E 3851 248 36788 124662

SE-U 3229 156 38037 124127

NL 3321 233 37070 124925

ES 4491 51 36169 124838

Included in Study (passed QC in at least 2 studies) 129464

Supplementary Table 2 Summary of SNPs failing Immunochip quality control metrics


Chr SNP POSITION GENE Allele STUDY P STUDY OR ACPA + P ACPA+ OR ACPA - P ACPA - OR Autoimmune disease

associations a) previously known associated loci

6 rs660895 32577380 HLA G lt1E-300 2265 lt1E-300 30299 154E-08 12083 Multiple

1 rs2476601 114377568 PTPN22 A 901E-62 15935 753E-77 17845 175E-04 11828 RA T1D SLE CD

5 rs71624119 55440730 ANKRD55 A 559E-20 08134 120E-11 08378 518E-12 07843 RA T2D

6 rs6920220 138006504 TNFAIP3 A 184E-10 11509 227E-13 12026 379E-02 10732 CeD RA SLE Ps T1D MS

PBC

4 rs12506688 26104113 RBPJ A 373E-10 11337 251E-10 11571 416E-02 10652 RA T1D

6 rs59466457 167537754 CCR6 A 347E-06 10903 274E-10 11455 644E-01 09869 CDRA AITD

2 rs13426947 191933254 STAT4 A 719E-10 11533 750E-09 11663 267E-03 11116 SLERA CeD PBC

9 rs2812378 34710260 CCL21 G 131E-08 11167 723E-10 11473 140E-02 10756 RA

20 rs6032662 44734310 CD40 G 172E-05 09104 137E-09 08564 710E-01 10123 RA MS

1 rs2843401 2528133 MMEL1 A 687E-07 09055 658E-09 08738 602E-01 09842 CeDRA UC MS AITD PBC

2 rs10209110 100672692 AFF3 A 113E-08 08996 679E-08 0891 001231 09317 RA T1D

2 rs34695944 61124850 REL G 414E-06 10918 258E-08 113 290E-01 10314 PsRA CeD CD UC

2 rs11571302 204742934 CTLA4 A 473E-07 09104 449E-08 08886 122E-01 09569 RA AITD T1DCeD

5 rs39984 102597292 GIN1 A 929E-08 08792 304E-06 08756 132E-04 08674 RA SLE

3 rs35677470 58183636 DNASE1L3 A 174E-07 11946 109E-06 12095 141E-02 11382 RA SLE

7 rs3807306 128580680 IRF5 C 248E-07 09093 190E-07 08947 222E-02 09374 SLERA UC PBC

22 rs3218251 37545505 IL2RB A 582E-06 10987 191E-07 11325 215E-01 10402 RAT1D

2 rs1980422 204610396 CD28 G 462E-06 11051 257E-07 11376 04738 10244 RA AITD T1DCeD


11 rs4938573 118741842 DDX6 G 397E-05 09072 531E-07 08703 631E-01 0983 RA SLE MS PBC CeD

2 rs6546146 65556324 SPRED2 A 191E-05 09205 798E-07 08952 505E-01 09805 RA

6 rs629326 159496713 TAGAP C 561E-03 09492 113E-06 08993 519E-01 10187 CeD RA CD T1D MS

9 rs10739580 123695282 TRAF1 G 456E-05 10846 168E-06 11152 953E-02 10527 RA SLE

10 rs10795791 6108340 IL2RA G 301E-06 10921 471E-06 11047 630E-02 10551 RA MST1D CD

8 rs4840565 11345545 BLK G 388E-06 10987 346E-04 10877 101E-04 11275 SLE RA

1 rs798000 117280696 CD2 G 892E-05 10802 619E-06 11081 443E-01 10234 RA MS

12 rs10683701 58092089 KIF5A - 439E-05 09221 231E-05 09072 403E-01 09751 RAMS

1 rs16843807 198745722 PTPRC C 110E-04 08905 248E-05 0863 638E-01 09787 RA

10 rs947474 6390450 PRKCQ G 251E-05 09038 398E-05 08872 01236 094 RA T1D CeD

1 rs11810143 161480649 FCGR2A G 934E-05 11153 174E-04 11339 01453 10709 RA CD SLE UC

6 rs6911690 106470963 PRDM1 G 517E-04 09004 169E-04 08692 04235 09605 CD RA SLE

4 rs78560100 123041471 IL2-21 C 448E-04 1131 118E-03 11425 000334 11802 CeD T1D RA UC

11 rs570676 36492191 TRAF6 A 481E-03 094 110E-03 093 046 097 RA b) newly associated loci on Immunochip

19 rs34536443 10463118 TYK2 G 270E-13 06885 225E-14 06208 116E-02 08246 MS CD Ps T1D SLE

23 rs13397 153248248 IRAK1 A 252E-12 12342 123E-12 12747 312E-05 1206 SLE T1D CeD

15 rs8026898 69991417 TLE3 A 222E-09 11327 137E-10 11662 370E-03 10969 BD

15 rs8043085 38828140 RASGRP1 A 163E-07 11193 140E-10 11713 372E-01 10303 T1D

1 rs2240336 17674402 PADI4 A 364E-08 09003 591E-09 08794 283E-02 09381 RA

1 rs8192284 154426970 IL6R C 132E-08 0897 157E-07 08903 244E-02 1 Asthma CHD

16 rs13330176 86019087 IRF8 A 931E-07 11131 403E-08 11475 772E-01 10099 SLE UC MS PBC

c) suggestive associated loci on Immunochip


7 rs75351767 37427351 ELMO1 G 294E-07 11604 385E-05 11473 595E-05 11917

17 rs12936409 38043649 IKZF3 A 372E-07 11029 690E-07 11158 113E-01 10483 CD UC T1D

6 rs72928038 90976768 BACH2 A 823E-07 11282 112E-04 11156 216E-03 11207 T1D CD

3 rs1875463 143165502 SLC9A9 A 151E-06 08996 288E-04 09119 475E-05 08709

10 rs12764378 63800004 ARID5B A 181E-05 10994 164E-06 11292 696E-01 10135

5 rs6579837 150434894 TNIP1 A 404E-05 11498 171E-06 12062 248E-02 11239 SLE Ps

14 rs911263 68753593 ACTN1 G 459E-04 09302 228E-06 08924 833E-01 09934 T1D

10 rs3802604 8102272 GATA3 G 507E-05 10813 368E-06 11085 217E-01 10372

18 rs62097857 12857758 PTPN2 A 446E-06 12224 880E-05 12171 114E-04 12825 CD CeD T1D

13 rs7993214 40350912 COG6 A 102E-04 09263 455E-06 09005 432E-01 09768

1 rs61828284 173299743 TNFSF18 TNFSF4 A 568E-05 08659 547E-06 08256 826E-01 09885 CD SLE

13 rs17230016 82338338 SPRY2 G 961E-06 08838 178E-04 0886 144E-03 08709

Supplementary Table 3 Summary of lead SNPs for RA associated loci on Immunochip Results are from 11475 RA cases versus 15870 controls (STUDY) or

for a subset of 7222 ACPA positive cases (ACPA +) or 3297 ACPA negative cases (ACPA -) versus the 15870 controls Associations reaching genome wide

significance emboldened and underlined co-ordinates based on GRCh37 assembly


Locus Chr All Immunochip +GWAS ACPA + Immunochip +GWAS bp SNP P bp SNP P known MMEL1 1 2528133 rs2843401 362E-08 2528133 rs2843401 724E-10

REL 2 61136129 rs13031237 140E-09 61136129 rs13031237 126E-11

SPRED2 2 65597671 rs11673987 349E-08 65598241 rs1858036 748E-10

AFF3 2 100806514 rs6712515 282E-11 100806514 rs6712515 200E-11

STAT4 2 191969879 rs10181656 234E-13 191921874 rs11893432 153E-11

CD28|CTLA4 2 204738919 rs3087243 748E-11 204738919 rs3087243 388E-11

RBPJ 4 26086569 rs17630466 567E-13 26104113 rs12506688 600E-13

ANKRD55 5 55440730 rs71624119 568E-20 55440730 rs71624119 120E-11

GIN1 5 102608924 rs2561477 652E-10 102608924 rs2561477 856E-08

TNFAIP3 6 138006504 rs6920220 424E-15 138006504 rs6920220 355E-18

TAGAP 6 159489791 rs212389 299E-05 159489791 rs212389 911E-09

CCR6 6 167540842 rs1571878 229E-08 167540842 rs1571878 123E-12

IRF5 7 128580680 rs3807306 712E-10 128580680 rs3807306 475E-10

CCL21 9 34710260 rs2812378 850E-09 34710260 rs2812378 126E-09

TRAF1 9 123683569 rs2269060 371E-07 123683569 rs2269060 173E-08

IL2RA 10 6108340 rs10795791 111E-09 6108340 rs10795791 119E-09

DDX6 11 118611781 rs10892279 295E-08 118611781 rs10892279 134E-10

CD40 20 44747947 rs4810485 220E-07 44747947 rs4810485 886E-11 new PADI4 1 17674108 rs2240339 257E-10 17674108 rs2240339 146E-10

POU3F1 1 38616871 rs883220 119E-07 38616871 rs883220 209E-08

IL6R 1 154426970 rs2228145 130E-08 154426970 rs2228145 158E-07

GATA3 10 8095340 rs2275806 738E-08 8095340 rs2275806 458E-08

ARID5B 10 63800004 rs12764378 100E-08 63800004 rs12764378 445E-10

CD5 11 60909581 rs595158 335E-08 60909581 rs595158 556E-06

RASGRP1 15 38828140 rs8043085 176E-08 38828140 rs8043085 482E-11

TLE3 15 69991417 rs8026898 603E-11 69991417 rs8026898 652E-12

IRF8 16 86019087 rs13330176 168E-07 86019087 rs13330176 530E-09

IKZF3 17 38062196 rs2305480 420E-09 38040763 rs2872507 279E-09

TYK2 19 10463118 rs34536443 269E-13 10463118 rs34536443 224E-14

RCAN1 21 35911599 rs2834512 431E-07 35911599 rs2834512 306E-08

RUNX1 21 36715761 rs9979383 503E-10 36715761 rs9979383 369E-08

Supplementary Table 4 Combined analysis of Immunochip results and imputed GWAS data from non-overlapping samples Results from the full Immunochip analysis (11475 RA cases versus 15870 controls) were added to non-overlapping ACPA positive samples (2363) from the latest GWAS meta analysis (All Immunochip +GWAS) In addition the ACPA positive GWAS samples were added to the ACPA positive Immunochip analysis (7222 cases versus 15870 controls) (ACPA+Immunochip +GWAS) Associations reaching genome wide significance emboldened and underlinedSNP not on GWASco-ordinates based on GRCh37 assembly


CHR SNP POS GENE META ACPA+

(P value) META ACPA +

(OR) META ACPA-

(P value) META ACPA-

(OR) META OR of OR (P value)

META OR of OR ( OR)

a) Loci more significant in ACPA positive at plt 005 level

1 rs2476601 114179091 PTPN22 923E-78 179 260E-04 118 244E-19 149

6 rs59466457 167457744 CCR6 477E-10 114 684E-01 099 100E-06 116

20 rs6032662 44167717 CD40 422E-09 086 831E-01 101 596E-06 085

15 rs8043085 36615432 RASGRP1 345E-10 117 363E-01 103 213E-04 114

6 rs629326 159416701 TAGAP 259E-06 090 717E-01 101 236E-04 089

11 rs4938573 118247052 DDX6 484E-07 087 596E-01 098 146E-03 089

15 rs77397211 36757788 RASGRP1 110E-03 115 524E-01 096 153E-03 121

2 rs34695944 60978354 REL 176E-08 113 359E-01 103 181E-03 110

1 rs2843401 2517993 MMEL1 800E-09 087 541E-01 098 188E-03 090

6 rs58721818 138285432 TNFAIP3 594E-12 146 899E-02 114 215E-03 127

2 rs6546146 65409828 SPRED2 603E-07 089 508E-01 098 220E-03 091

19 rs34536443 10324118 TYK2 303E-14 062 750E-03 082 295E-03 077

16 rs13330176 84576588 IRF8 872E-08 114 726E-01 101 340E-03 111

10 rs12722508 6128749 IL2RA 201E-05 085 891E-01 101 367E-03 086

1 rs798000 117082219 CD2 431E-06 111 469E-01 102 727E-03 109

10 rs12764378 63470010 ARID5B 900E-07 113 656E-01 102 881E-03 110

2 rs11571302 204451179 CTLA4CD28 456E-08 089 105E-01 096 890E-03 092

6 rs6920220 138048197 TNFAIP3 309E-13 120 220E-02 108 986E-03 110

4 rs932036 25699960 RBPJ 355E-10 116 176E-02 108 178E-02 108

17 rs2872507 35294289 GSDML 131E-06 111 239E-01 103 276E-02 107

9 rs2812378 34700260 CCL21 518E-10 115 117E-02 108 356E-02 107

21 rs2834512 34833469 RCAN1 293E-04 088 507E-01 097 441E-02 091

17 rs12936409 35297175 GSDML 771E-07 111 113E-01 105 452E-02 106

b) Significant in both ACPA positive and negative and no significant difference at plt 005 level

5 rs71624119 55476487 ANKRD55 171E-11 084 623E-12 079 825E-02 107


8 rs4840565 11382954 BLK 343E-04 109 853E-05 113 332E-01 097

21 rs9979383 35637631 RUNX1 315E-05 091 990E-05 089 554E-01 102

5 rs39984 102625191 GIN1 383E-06 088 165E-04 087 761E-01 101

1 rs2014863 197076224 PTPRC 874E-04 108 835E-04 110 369E-01 097

2 rs932169 191637523 STAT4 239E-02 109 116E-03 118 120E-01 092

19 rs3176767 10310751 ICAM3 271E-05 111 191E-03 111 859E-01 101

4 rs78560100 123260921 IL2_21 117E-03 114 214E-03 118 641E-01 097

2 rs13426947 191641499 STAT4 494E-09 117 262E-03 111 170E-01 105

11 rs595158 60666157 CD5 176E-05 110 597E-03 108 642E-01 101

3 rs35677470 58158676 DNASE1L3 150E-06 121 928E-03 115 516E-01 104

Supplementary Table 5 Comparison of the known and newly discovered confirmed RA susceptibility loci in ACPA positive (7222 cases versus 15870 controls) and ACPA negative disease (3297 cases versus 15870 controls) on Immunochip OR of OR is a formal test to assess the difference in association between the two serological forms of disease


REGION Lead GRAIL CANDIDATE

Chromosome name Position on Chromosome (bp) SNP p-value GENE

1 2528133 rs2843401 709E-06 TNFRSF14

1 17674537 rs2240335 404E-02 PADI4

1 38616871 rs883220 967E-01 POU3F1

1 114377568 rs2476601 287E-05 PTPN22

1 117263138 rs11586238 369E-10 CD2

1 154426970 rs2228145 305E-05 IL6R

1 161467042 rs12746613 433E-06 FCGR2B

1 167411384 rs864537 220E-11 CD247

1 198700442 rs10919563 125E-10 PTPRC

2 61136129 rs13031237 218E-06 REL

2 65595586 rs934734 144E-01 SPRED2

2 100806940 rs11676922 537E-01 AFF3

2 191935804 rs10168266 961E-09 STAT4

2 204610396 rs1980422 277E-12 CD28

2 204738919 rs3087243 142E-11 ICOS

3 58556841 rs13315591 895E-01 DNASE1L3

4 26104113 rs12506688 739E-01 RBPJ

4 123509421 rs6822844 432E-09 IL2

5 55438580 rs6859219 100E+00 ANKRD55

5 102608924 rs2561477 936E-01 GIN1

6 106568034 rs548234 180E-04 PRDM1

6 138002637 rs10499194 212E-04 TNFAIP3

6 159482521 rs394581 162E-05 TAGAP

6 167540842 rs1571878 426E-07 CCR6

7 128594183 rs10488631 326E-04 IRF5

8 11343973 rs2736340 259E-02 BLK

9 34743681 rs951005 960E-06 CCL21

9 123640500 rs1953126 208E-06 TRAF1

10 6099045 rs2104286 441E-10 IL2RA

10 6393260 rs4750316 422E-08 PRKCQ

10 8095340 rs2275806 726E-05 GATA3

10 63800004 rs12764378 884E-01 ARID5B

11 36525293 rs540386 671E-11 RAG1

11 60909581 rs595158 399E-11 CD5

11 118611781 rs10892279 919E-01 DDX6

12 57968715 rs1678542 658E-01 B4GALNT1

15 38828140 rs8043085 682E-08 RASGRP1

15 69991417 rs8026898 943E-01 KIF23

16 86019087 rs13330176 300E-07 IRF8

17 38040763 rs2872507 247E-05 IKZF3

19 10295433 rs4804493 751E-01 DNMT1


20 44734310 rs6032662 438E-10 CD40

21 35911599 rs2834512 197E-01 RCAN1

21 36715761 rs9979383 914E-02 RUNX1

21 43836186 rs11203203 106E-01 UBASH3A

22 21982892 rs2298428 964E-01 YDJC

22 37544810 rs3218253 100E-08 IL2RB

Supplementary Table 6 Results from a GRAIL analysis indicating the most likely RA susceptibility

gene in regions associated at genome wide association levels


Locus Gene Index Secondary effect LD with index

1-SNP model

Haplotypic risk

SNP alleles

(Mm)

MAF p OR SNP alleles

(Mm)

MAF p OR (r2Dacute) Vs 2-SNP haplotype Freq OR

2q33 CD28 rs1980422 AG 023 337E-09 115 rs55686954 GA 004 427-E05 08 0015100 327E-05 AA 004 base

AG 072 126

GG 023 143

GA 00002 -

15q14 RASGRP1 rs8043085 CA 023 478E-12 118 rs77397211 AG 007 113E-04 117 0001018 125E-04 CA 070 base

CG 006 117

AA 023 118

AG 001 139

2p16-p15

REL rs34695944 AG 037 854E-11 115 rs78404002 GA 005 912E-05 078 0023093 739E-05 AA 004 base

AG 058 12

GG 038 136

GA 0005 -

2q32 STAT4 rs7574865 CA 022 961E-09 115 rs3024921 TA 006 666E-06 118 0021100 527E-06 CT 071 base

AT 024 115

CA 006 120

AA 0 -

6q23 TNFAIP3 rs6920220 GA 022 124E-14 120 rs58721818 GA 003 436E-08 134 0030047 580E-08 GG 076 base

AG 021 118

GA 002 137

AA 002 155

19p13 TYK2 rs34536443 CG 005 157E-14 063 rs12720356 AC 010 122E-05 085 0004100 102E-05 CA 088 base

CC 009 085

GA 004 062

GC 0 -

Supplementary Table 7 Haplotype analysis of six loci with additional independent effects on Immunochip


Chr POS Gene region

Lead SNP Low MAF

SNP

MAF

UNAFF

MAF

AFF

P OR r2

to lead

Location REG POT7X

CONS 17WA

Y

2 61320107 REL rs78404002a rs78404002 005 004 342E-05 083 lead INTRONIC 000 000

2 61391558 REL rs17008218 005 004 439E-05 083 1 INTRONIC 000 008

2 61581489 REL rs17009924 005 004 947E-05 084 092 INTRONIC 000 000

2 61629635 REL rs78534076 005 004 491E-05 083 093 INTERGENIC 000 003

2 204294760 CTLA4 rs55686954a rs55686954 004 003 120E-07 077 lead INTRONIC 015 000

6 138178293 TNFAIP3 rs58721818a rs117267050 003 004 631E-08 131 092 INTERGENIC 000 000

6 138239199 TNFAIP3 rs5029949 003 004 351E-08 131 091 INTRONIC 000 001

6 138269057 TNFAIP3 rs7752903 003 004 315E-08 132 095 INTERGENIC 000 0006




6 138285432 TNFAIP3 rs58721818 003 004 407E-09 134 lead INTERGENIC 011 0035

19 10288721 TYK2 rs34536443 rs74956615 006 004 521E-11 074 1 3rsquo UTR 000 0998

19 10324118 TYK2 rs34536443 005 003 270E-13 069 lead Non Synonymous 039 019

Supplementary Table 8 Low MAF (lt5) SNPs (in either cases or controls) in strong LD (r2gt09) with a lead SNP from Immunochip analysis a=Lead SNP reported for these regions is an independent affect in region after conditioning on most associated SNP


Supplementary Table 9 Comparison of lead SNPs for previously confirmed RA loci indentified by GWAS and Immunochip analysis where the focus of

association has moved (r2lt08)Actual SNP not found on Immunochip Perfect proxy (r2 and Drsquo = 1) used for Immunochip comparison a = rs9813011 b=

rs5030437 = Result from ACPA positive analysis

GWAS IMMUNOCHIP

Index SNP GENE CHR MAF P OR Index SNP MAF P OR GWAS index SNP r2 D

P OR

rs13315591a PXK 3 009 46x10-8 129 rs35677470 008 17 X 10-07 119 028 103 027 058

rs10488631 IRF5 7 011 42x10-11 119 rs3807306 049 19 X 10-07 089 18 X 10-05 11 02 1

rs934734 SPRED2 2 049 53x10-10 113 rs6546146 038 80 X 10-07 09 30 X 10-04 107 053 095

rs3761847 TRAF1 9 043 21x10-7 113 rs10739580 033 17 X 10-06 112 17 X 10-04 107 074 1

rs2104286 IL2RA 10 027 2x10-3 092 rs10795791 04 30 X 10-06 109 10 X 10-04 091 025 1

rs11586238 CD2 1 024 1x10-5 113 rs798000 034 62 X 10-06 111 30 X 10-03 107 033 072

rs10919563 PTPRC 1 013 2x10-4 088 rs2014863 036 21 X 10-05 109 77 X 10-04 091 007 1

rs1678542 KIF5A 12 038 2x10-4 091 rs10683701 033 23 X 10-05 09 10 X 10-03 093 027 058

rs548234 PRDM1 6 033 97x10-5 11 rs6911690 012 12 X 10-04 087 002 104 01 1

rs6822844 IL2-IL21 4 018 7x10-4 09 rs78560100 007 58 X 10-04 113 001 094 002 1

rs540386b TRAF6 11 014 3x10-4 088 rs570676 038 21 X 10-03 093 007 095 018 1


Before Immunochip Results from Immunochip

Gene Chr 01cM localisation

Region size

SNP LD region r2gt09

Region size

All SNPS (ns) in r2gt09 region

LD SNPS (ns)

r2gt09

Localization of LD region (r2gt09)

relative to nearest genes

a) Known loci on Immunochip

PTPN22 1p13 113863087-

114527968

665kb

rs2476601b 114303808-114377568

7376kb 682 (27) 2 (1) Complete RSBN1 Exon 14

to 5262kb 3 of PTPN22

ANKRD55 5q11 55414956-

55447909

33kb

rs71624119a 55440730-55442249

152kb 19 (0) 2 (0) Intron 6 of ANKRD55

TNFAIP3 6q23 137896596-

138125335

229kb

rs6920220b 137959235-138006504

4727kb 761 (0) 9 (0) 18185kb 5 of TNFAIP3

TNFAIP3 6q23 137896596-

138125335

229kb

rs58721818g 138178293-

138243739

6545kb 835 (38) 7 (0) TNFAIP3

RBPJ 4p15 26028805-

26134465

106kb

rs932036a 26085480-26128710

4323kb 486 (0) 25 (0) 3637kb 5 of RBPJ

CCR6 6q27 167355854-

167547954

192kb

rs59466457b 167526096-

167540842

1475kb 234 (0) 6 (0) Intron 1 of CCR6

STAT4 2q32 191873553-

192007734

134kb

rs13426947a 191900449-191935804

3536kb 398 (11) 10 (0) Intron 5 to 18 of STAT4

STAT4 2q32 191873553- 134kb rs932169e 191929278-191929278

1bp 1 (0) 1 (0) Intron 8 of STAT4


192007734

CCL21 9p13 34649442-

34974974

325kb rs2812378b 34707373-34710338

297kb 41 (4) 3 (0) CCL21

CD40 20q13 44594228-

44784336

190kb

rs6032662b 44730245-44747947

1770kb 239 (1) 10 (0) 1667kb 5 to intron 1 of CD40

MMEL1 1p36 2406888-

2785671

378kb

rs2843401b 2516781-2709164

19238kb

4571 (73)

85 (1)

Complete MMEL1 C1ORF93 TTC34

AFF3 2q11 100544954-

101038647

493kb

rs10209110a 100640432-100730111

8968kb 990 (2) 18 (0) 5 region to intron 2 of AFF3

REL 2p16 60914729-

61864047

949kb

rs34695944b 61072664-61164331

9167kb 876 (18) 14 (0) Complete REL

REL 2p16 60914729-

61864047

949kb

rs78404002g 61466603-61776131

30953kb

3579 (24)

5 (0)

7823kb 5 to intron 53 of

USP34 SNORA70B XPO1

31596kb 3 of REL CTLA4 2q33 204678417-

204816382

138kb

rs11571302b 204738919-204745003

608kb 83 (0) 4 (0) 236bp 3 of CTLA4 5647kb 5 of ICOS

GIN1 5q21 102098582-

102711659

613kb

rs39984a 102595778-102625335

2956kb

385 (7)

40 (0)

Intron 1 to 1097kb 3 of C5orf30

13992kb 5of GIN1

PXK 3p14 58154177-

58549297

395kb

rs35677470a 58181499-58183636

214kb 37 (2) 2 (1) Exon 8 to intron 9 of DNASE1L3

13497kb 5 of PXK

IRF5 7q32 128549568- 228kb rs3807306b 128580680-128580680

1bp 1 (0) 1 (0) Intron 1 of IRF5


128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884

8289kb 1169 (0) 48 (0) Complete SETP16 114kb 5 of DDX6

SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300

4198kb 585 (7) 13 (0) Intron 1 to intron 4 of SPRED2

TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485

1410kb 267 (0) 5 (0) 1313kb 5 to intron 1 of BLK

CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)

745kb 3 of CD28 9794kb 5 of CTLA4

CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515

1bp 1(0) 1(0) Intron 1 of CD28 14599kb 5 of CTLA4


PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094

7026kb 945 (8) 104 (0) snoU135290kb 5 to intron 5 of OS9

5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649

1677kb 230 (13) 17 (0) 1134kb 5 to exon 5 of FCGR2A

PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624

3356kb 434 (14) 11 (0) Intron 3 to 2251kb 3 of TRAF6

b) Novel loci on Immunochip

TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274

6455kb 973 (124) 3 (1) 4796kb 5 to exon 13 of RAVER1 complete ICAM3

complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778

288kb 58 (8) 16 (1) Intron 1 to intron 2 of ICAM3 1143kb 3 of TYK2

IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248

519kp 406 (52) 3 (0) 5rsquo to exon 2 of TMEM187 HCFC1

25kb 3rsquo of IRAK1


TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283

954kb 132 (4) 10 (1) Intron 6 to intron 9 of IL6R

IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8

(c) Novel loci adding GWAS data

ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912

16854kb 1935 (70) 49 (1) IKZF3GSDMB Intron 1 to

16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1

CD5 11q12 60723898- 112kb rs595158c 60888001- 3463kb 475 (35) 30 (1) Intron 5 to 2731kb 3


60836519 60922634 of CD5 Intron 1 to 973kb 3of VPS37C

GATA3 10p14 rs2275806d 8095340-8097368

203kb 36 (0) 2 (0) 227bp 5 to exon 2 of GATA3

Supplementary Table 10 Localisation of association signals from GWAS and Immunochip for non-HLA RA loci Previously indentified loci are shown with the

most significantly associated SNP on Immunochip (2a) Novel loci are shown with either the best SNP on Immunochip (Table 2b) if lt5x10-8 or from the

most associated SNP from the combined analysis of GWAS and Immunochip data (2c) a indicates the data is from all RA samples on Immunochip b is data

from Immunochip for ACPA positive individuals c is data from adding GWAS samples and RA Immunochip data and d is from ACPA positive Immunochip and

GWAS data SNPs in bold represent secondary effects at loci Secondary effects are defined as plt5x10-4 with low evidence of LD between SNPs (r2lt005)

MAFgt1 and a p value that didnrsquot vary substantially on conditioning e f and g indicate secondary effects where the effect was seen in Immunochip data

from all samples ACPA positive samples or both respectivelyco-ordinates based on GRCh37 assembly region not included for dense mapping on

Immunochip


REGION SNP CHR POS r2 with index SNP Location REGPOT7X CONS 17WAY

MAF

Intergenic SNPs with the strongest evidence for regulatory potential

rs10739580 TRAF1 rs1930786 9 122731290 100 UPSTREAM 0798 0000 044

rs4840565 BLK rs922483 8 11389321 097 5rsquo UTR 0511 0005 033

rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026

rs10739580 TRAF1 rs881375 9 122692719 097 INTERGENIC 0407 0800 043

rs39984 GIN1 rs2288787 5 102628605 100 INTRONIC 0399 0024 034

Intergenic SNPs with the strongest evidence for conservation

rs6911690 PRDM1 rs9320143 6 106542674 096 INTERGENIC 0342 1000 013

rs12936409 IKZF3 rs12946510 17 35165903 090 DOWNSTREAM 0341 1000 049


rs10683701 KIF5A rs774891 12 56354838 095 NON-CODING GENE 0209 1000 033

rs78560100 IL2-IL21 rs62323937 4 123337405 096 INTRONIC 0000 1000 008

rs12764378 ARID5B rs12764378 10 63470010 Index INTRONIC 0000 1000 018



rs34536443 TYK2 rs74956615 19 10288721 100 3rsquo UTR 0000 0998 002

Intergenic snps with evidence for both conservation (gt05) and regulatory potential (gt01)







rs12936409 IKZF3 rs10445308 17 35191573 094 INTRONIC 0169 0989 048

rs34695944 REL rs13017599 2 61017835 100 DOWNSTREAM 0231 0978 037

rs34695944 REL rs67574266 2 60962333 100 5rsquo UTR 0345 0975 037

rs78560100 IL2|IL21 rs62321698 4 123500153 095 INTRONIC 0221 0973 007

rs6920220 TNFAIP3 rs6927172 6 138043868 100 INTERGENIC 0229 0965 016

rs78560100 IL2|IL21 rs79212788 4 123648588 093 INTERGENIC 0108 0933 008

rs39984 GIN1 rs556560 5 102651823 091 INTERGENIC 0175 0818 036



Supplementary Table 11 Intergenic potential causal SNPs Intergenic SNPs in strong LD (r2gt09) with a lead SNP on Immunochip with evidence for either strong regulatory potential (regpot7x gt035) or conservation (cons17way gt0998) or evidence for both (regpot7x gt01 cons17way gt05)

Gene1 SNP1 Gene2 SNP 2 p-value Z-score

MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494

CTLA4 rs11571302 RASGRP1 rs8043085 489E-04 3487

Supplementary Table 12 Pairwise interactions remaining statistically significant after Bonferroni correction


Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo

MMEL1a rs4445406 034 54 times 10minus12 087 rs2843401 033 66x10

-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1

STAT4a rs6715106 006 84 times 10minus9 079 rs13426947a

rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1

STAT4 Signal 2 rs6752770 029 13 times 10minus6 110 rs13426947a

rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1

CD28a rs1980422 023 1`4 times 10minus15 119 rs11571302a

rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1

CTLA4 Signal 2 rs34037980 022 16 times 10minus5 091 rs11571302a

rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002

CD28 Signal 3 rs10207814 004 13 times 10minus4 120 rs11571302a

rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1

IL2 _IL21a rs13132308 016 19 times 10minus38 071 rs78560100 007 58x10

-4 113 001 094 002 099

IL2 _IL21 Signal 2 rs62323881 007 86 times 10minus5 115 rs78560100 007 58x10-4

113 9x10-4

112 1 1

BACH2b rs7753008 038 27 times 10minus7 110 rs72928038 018 82x10

-7 113 78x10

-3 105 02 086

TNFAIP3a rs17264332 021 50 times 10minus30 129 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047

TNFAIP3 Signal 2 [imm_6_ 138043754]

rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1

TAGAPa rs182429 043 85 times 10minus16 116 rs629326 041 11x10

-6 09 002 097 044 069

TAGAP Signal 2 rs1107943 007 28 times 10minus6 118 rs629326 041 11x10-6

09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099

PVT1b rs10808568 026 22 times 10minus5 091 rs6651252 013 20x10

-5 088 005 096 002 019

PRKCQa rs2387397 023 19 times 10minus8 088 rs947474a

rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036

DDX6a rs10892258 024 17 times 10minus11 086 rs4938573 018 53x10

-7 087 15x10

-4 091 062 088

PTPN2b rs11875687 015 19 times 10minus10 117 rs62097857 004 446x10

-6 122 1x10

-4 11 0008 1

PTPN2 Signal 2 rs62097857 004 52 times 10minus5 120 rs62097857 004 446x10-6

122 45x10-6

122 1 1

IRAK1a rs13397 013 27 times 10minus8 118 rs13397 012 27 times 10minus8 118 25x10

-12 123 1 1

Supplementary Table 14 Comparison of Immunochip dense mapping data in celiac disease and RA for loci that are either confirmed at genome-wide

significance in both diseases (plt5x10-8) a or are confirmed in celiac disease and highly suggestive (plt2 x10-5) in RA bAll MAF in controls

SNP Study P-

value λGC corrected

(123) Gender_covariate

rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08

Supplementary Table 15 Results for novel loci on Immunochip after λGC and gender correction


Supplementary Figure 1 QQ plot of observed versus expectedresults for the meta-analysis of the six sample collections Red ndashexcluding the MHC region and all other previously identifiedsusceptibility loci Orange ndash excluding the MHC region and all otherpreviously identified and newly discovered loci


Supplementary Figure 2 GRAIL-VIZ plots for the confirmed rheumatoid arthritis genes Associated genomic regions are along the outer circle with the inner circle showing the individual genes The thickness of lines connecting genes shows the strength of the GRAIL signal


chr12384956minus2796789 (acpa_pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1

24 25 26 27Position on chr1 (Mb)


0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6

1748 175 1752 1754 1756Position on chr1 (Mb)


0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45

1169 117 1171 1172 1173 1174Position on chr1 (Mb)

chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10

15262 15264 15266 15268 1527 15272 15274Position on chr1 (Mb)


chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2

ATP6V1G3 PTPRC MIR181B1

MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A

605 61 615Position on chr2 (Mb)


0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2

RNASET2 FGFR1OP CCR6 GPR31

TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2

IL15RA IL2RA RBM17 PFKFB3


chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2

PRR5L TRAF6 RAG1 RAG2

C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96



Supplementary Figure 3 Regional association plots of immunochip datafor all previously known and novel regions The linkage disequilibrium basedlocalisation (r2 gt= 09 with index SNP) of the association signal is indi-cated in the gene track by a light blue box SNP annotation provided byLocusZoom databases (triangle - framestopsplice site inverted triangle -nonsynonymous box - synonymousUTR star - transcription factor bindingsite crossed-box - multi-species conserved site)

10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5


Supplementary Figure 4 We evaluated the cell-specific expression of genes contained in 47 RA loci in 223 murine immune-cell types To do this we compared specific expression of genes within RA loci to genes within randomly selected loci matched for gene number We show the Bonferroni-corrected p-value (005223 = 224x10-4) with a dotted line We labeled all cell types that are significant after adjusting for multiple hypothesis at the top of the plot The four most significant cell types (plt10-7 CD4 memory T-cells in subcutaneous lymph node and spleen and CD44highCD62low CD4 memory T-cells in subcutaneous lymph node and spleen) are labeled in red


SNPs associated to RA in this study

N=50

Genotyped or imputed in eQTL dataset

Yes n=26

No n=24

Directly accessed for eQTL effect

Proxy (r2gt08) present in 1000genomes

Yes n=12

Proxy accessed for eQTL effect

SNPs not included to eQTL analysis

No n=12

Supplementary Figure 5 Scheme of SNP selection for eQTL analysis Nature Genetics doi101038ng2369

Supplementary Note

Sample collections

United Kingdom (UK) The UK Manchester cohort of patients with rheumatoid arthritis (n =4752)

were recruited from across the UK All cases were European ancestry of Northern European descent

and all fulfilled the 1987 American College of Rheumatology classification criteria modified for

genetic studies All participants were recruited after providing informed consent and the study was

approved by the North West Research Ethics Committee (MREC 99884) Serum RF and ACPA

antibody titre were measured using commercially available kits [RF-PAIA Immunoturbidimetric Assay

for rheumatoid factor DiastatTM ACPA Kit (Axis-Shield Diagnostics Limited UK)] Patients with titres

_40 unitsml and _5 unitsml were defined as positive for RF and ACPA antibodies respectively

United States (US) Cases from the US have been studied and reported on previously and include

three major datasets totalling 2740 rheumatoid arthritis cases submitted for genotyping on the

Immunochip The NARAC cases (n=1312 69 ACPA+) are largely derived from families with

rheumatoid arthritis affected sibling pairs supplemented with singleton subjects whose siblings did

not meet criteria for study entry US singleton rheumatoid arthritis subjects and subjects from trio

families18 19 A second selected group of all ACPA+ rheumatoid arthritis subjects (n=660) included

patients recruited by Dr Frederick Wolfe in his practice as well as rheumatoid arthritis subjects

enrolled in a published inception cohort as well as subjects followed in the National Database for

Rheumatic Diseases directed by Dr Wolfe20 21 A third cohort of subjects (N=768 44 ACPA+) were

derived from an inception cohort study SONORA as described previously22

Sweden EIRA (SE-E) Swedish cohort consisting of 2955 incidence rheumatoid arthritis cases and

2086 matched controls from Swedish epidemiological and genetic study of rheumatoid arthritis

(EIRA) study which is described elsewhere23 All rheumatoid arthritis patients met the American

College for Rheumatology 1987 (ACR-87) revised criteria for rheumatoid arthritis and blood samples

were collected at 19 rheumatology units across Sweden (mainly middle and south of country)

Controls were matched by date of birth sex and residence area were invited by mail and were

asked to leave a blood sample in local ward Ethics permit was received and informed consent was

registered according to the current Swedish law

Sweden Umea (SE-U) The Swedish Umea cohort is an inception cohort of patients fulfilling the

American College of Rheumatology (ACR) 1987 criteria for classical rheumatoid arthritis (Arnett et al

1988) from the four most northern counties of Sweden The controls are randomly selected

matched for age and sex donors to the population based Medical Biobank of Northern Sweden The

patients and controls have the same ethnic background Detection of Anti-Cyclic citrullinated

peptide antibodies was analysed using enzyme-linked immunoassays (Euro-Diagnostica Malmouml

Sweden) according to manufacturerrsquos instructions Cut-off for positivity was 25 AUml The regional


Ethics Committee at the University Hospital of Umearing approved this study and all participants gave

their written informed consent

The Netherlands (NL) Patients visiting the out-patient clinic with arthritis in at least one joints and

symptom duration of less than two year were included in the Leiden-Early Arthritis Clinic (Leiden-

EAC) Patients that were diagnosed with rheumatoid arthritis according to the 1987 ACR criteria

within one year after inclusion in the Leiden-EAC were included in the current study (n=648)The

study was approved by the local ethical committee and all patients gave their informed consent

Controls were obtained from the blood donors and have been described3

Spain (ES) The Spanish cohort of rheumatoid arthritis patients (n=914) were recruited across Spain

fulfilling the American College of Rheumatology 1987 classification criteria The controls (n=447)

were obtained from the Spanish DNA Bank matched by age and sex Both patients and controls

were white of Southern European descent All participants were recruited after providing informed

consent

Members of the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate

(BRAGGSS)

Steering Committee members Prof Anne Barton Professor John Isaacs Prof Ann Morgan Prof

Gerry

Wilson Dr Kimme Hyrich

Basingstoke amp North Hampshire NHS Foundation Trust (Dr R K Moitra Dr P J Prouse Dr D J Shawe)

Cambridge University Hospitals NHS Foundation Trust (Dr A J Crisp Prof J S H Gaston Dr F C Hall

Dr B L Hazleman Dr J R Jenner Dr M S Lillicrap Dr A Ostor Dr B Silverman Dr C Speed)

Central Manchester University Hospitals NHS Foundation Trust (Dr I N Bruce Dr K Hyrich Dr P Ho Dr

R Gorodkin)

County Durham and Darlington NHS Foundation Trust (Dr D Armstrong Dr A J Chuck Dr S

Hailwood Dr N Kumar)

Derby Hospitals NHS Foundation Trust (Dr L J Badcock Dr C M Deighton Dr S C OReilly Dr N Raj

Dr M R Regan DrG D Summers Dr R A Williams)

Doncaster And Bassetlaw Hospitals NHS Foundation Trust (Dr J R Lambert Dr R Stevens Dr C

Wilkinson)

Gateshead Health NHS Foundation Trust (Dr J Hamilton Dr C R Heycock Dr C A Kelly Dr V

Saravanan)


Hereford Hospitals NHS Trust (Dr D H Rees Dr R B Williams)

Leeds Teaching Hospitals NHS Trust (Dr S Bingham Prof P Emery Dr A Morgan Prof H A Bird Prof

P G Conaghan Dr C T Pease Dr R J Wakefield)

Mid-Staffordshire NHS Foundation Trust (Dr S V Chalam Dr D Mulherin Dr T Price Dr T Sheeran

Dr S Venkatachalam)

NorfolkampNorwich University Hospital NHS Foundation Trust (Dr K Gaffney Prof A J Macgregor Dr T

Marshall Dr P Merry Prof D G I Scott)

Northumbria Healthcare NHS Foundation Trust (Dr F N Birrell Dr P R Crook)

Pennine Acute Hospitals NHS Trust (Dr B Harrison Dr M Pattrick Dr H N Snowden Dr A P Bowden

Dr E E Smith Dr P Klimiuk Dr D J Speden)

Peterborough and Stamford Hospitals NHS Foundation Trust (Dr N J Sheehan Dr N E Williams Dr S

Dahiya)

Portsmouth Hospitals NHS Trust (Dr R G Hull Dr J M Ledingham Dr F Mccrae Dr M R Shaban Dr

A L Thomas Dr S A Young Min)

Queen Maryrsquos Sidcup NHS Trust (Dr A N Bamji Dr N T Cheung)

Sandwell and West Birmingham Hospitals NHS Trust (Prof C D Buckley Dr D C Carruthers Dr R

Elamanchi Dr P C Gordon Dr K A Grindulis Dr F Khattak Dr K Raza Dr DSitunayake)

Sheffield Teaching Hospitals NHS Foundation Trust (Drs S Till M Akil R Tattersall R Kilding L Dunley

J BoultonT Tait Prof A G Wilson Prof D E Bax)

South Tees Hospitals NHS Foundation Trust (Dr F Clarke Dr J N Fordham Dr M J Plant Dr Tuck Dr

S K Pathare)

Southampton University Hospitals NHS Trust (Dr C J Edwards Dr N K Arden Dr R D Armstrong Dr A

Calogeras Prof C Cooper Dr B K S Davidson Dr E M Dennison)

St Helens and Knowsley Hospitals NHS Trust (Dr V E Abernethy Dr A R Clewes Dr J K Dawson Dr M

Lynch)

The Dudley Group of Hospitals NHS Foundation Trust (Prof G Kitas Dr J P Delamere Dr N Erb Dr R

Klocke Dr A J Whallett)

The Newcastle upon Tyne Hospitals NHS Foundation Trust (Mr P Crook Dr H E Foster Dr B Griffiths

Dr I D Griffiths Dr M L Grove Prof J D Isaacs DR L Kay Dr W F Ng Dr A Myers Dr P N Platt Dr D J

Walker)

University Hospital Birmingham NHS Foundation Trust (Dr Bowman Dr P Jobanputra Dr R W Jubb

Dr E C Rankin)

University Hospital of North Staffordshire NHS Trust (Dr P T Dawes Dr C M Dowson Dr A Hassell

Prof E M Hay Dr S Kamath Dr J Packham Dr R S Sandhu Dr M F Shadforth)


University Hospitals of Morecambe Bay NHS Trust (Dr M Bukhari Dr W N Dodds Dr J P Halsey Dr

W S Mitchell)

West Suffolk Hospitals NHS Trust (Dr D T OrsquoReilly)

Whipps Cross University Hospital NHS Trust (Dr S P Donnelly Dr D Doyle Dr A Hakim Dr J G

Lanham Dr H I S Tahir Dr J Rathi)

Worcestershire Acute Hospitals NHS Trust (Dr A Rai Dr I F Rowe Dr A Prabu Dr C A M Buckley)

Membership of the Wellcome Trust Case Control Consortium (WTCCC)

Management Committee

Paul R Burton1 David G Clayton2 Lon R Cardon3 Nick Craddock4 Panos Deloukas5 Audrey

Duncanson6 Dominic P Kwiatkowski35 Mark I McCarthy37 Willem H Ouwehand89 Nilesh J

Samani10 John A Todd2 amp Peter Donnelly (Chair)11

Data and Analysis Committee

Jeffrey C Barrett3 Paul R Burton1 Dan Davison11 Peter Donnelly11 Doug Easton12 David Evans3

Hin-Tak Leung2 Jonathan L Marchini11 Andrew P Morris3 Chris C A Spencer11 Martin D Tobin1

Lon R Cardon (Co-Chair)3 amp David G Clayton (Co-Chair)2

UK Blood Services and University of Cambridge Controls

Antony P Attwood58 James P Boorman89 Barbara Cant8 Ursula Everson13 Judith M Hussey14

Jennifer D Jolley8 Alexandra S Knight8 Kerstin Koch8 Elizabeth Meech15 Sarah Nutland2

Christopher V Prowse16 Helen E Stevens2 Niall C Taylor8 Graham R Walters17 Neil M Walker2

Nicholas A Watkins89 Thilo Winzer8 John A Todd2 amp Willem H Ouwehand89

1958 Birth Cohort Controls

Richard W Jones18 Wendy L McArdle18 Susan M Ring18 David P Strachan19 amp Marcus Pembrey1820

Bipolar Disorder

Gerome Breen21 David St Clair (Aberdeen)21 Sian Caesar22 Katherine Gordon-Smith2223 Lisa Jones

(Birmingham)22 Christine Fraser23 Elaine K Green23 Detelina Grozeva23 Marian L Hamshere23

Peter A Holmans23 Ian R Jones23 George Kirov23 Valentina Moskvina23 Ivan Nikolov23 Michael C

ODonovan23 Michael J Owen23 Nick Craddock (Cardiff)23 David A Collier24 Amanda Elkin24 Anne

Farmer24 Richard Williamson24 Peter McGuffin (London)24 Allan H Young25 amp I Nicol Ferrier

(Newcastle)25


Coronary Artery Disease

Stephen G Ball26 Anthony J Balmforth26 Jennifer H Barrett26 D Timothy Bishop26 Mark M Iles26

Azhar Maqbool26 Nadira Yuldasheva26 Alistair S Hall (Leeds)26 Peter S Braund10 Paul R Burton1

Richard J Dixon10 Massimo Mangino10 Suzanne Stevens10 Martin D Tobin1 John R Thompson1 amp

Nilesh J Samani (Leicester)10

Crohns Disease

Francesca Bredin27 Mark Tremelling27 Miles Parkes (Cambridge)27 Hazel Drummond28 Charles W

Lees28 Elaine R Nimmo28 Jack Satsangi (Edinburgh)28 Sheila A Fisher29 Alastair Forbes30 Cathryn

M Lewis29 Clive M Onnie29 Natalie J Prescott29 Jeremy Sanderson31 Christopher G Mathew

(London)29 Jamie Barbour32 M Khalid Mohiuddin32 Catherine E Todhunter (Newcastle)32 John C

Mansfield32 Tariq Ahmad33 Fraser R Cummings33 amp Derek P Jewell (Oxford)33

Hypertension

John Webster (Aberdeen)34 Morris J Brown35 David G Clayton (Cambridge)2 G Mark Lathrop

(Evry)36 John Connell37 Anna Dominiczak (Glasgow)37 Nilesh J Samani (Leicester)10 Carolina A

Braga Marcano38 Beverley Burke38 Richard Dobson38 Johannie Gungadoo38 Kate L Lee38 Patricia B

Munroe38 Stephen J Newhouse38 Abiodun Onipinla38 Chris Wallace38 Mingzhan Xue38 Mark

Caulfield (London)38 amp Martin Farrall (Oxford)39

Rheumatoid Arthritis

Anne Barton40 The Biologics in RA Genetics and Genomics (BRAGGS)55 Ian N Bruce40 Hannah

Donovan40 Steve Eyre40 Paul D Gilbert40 Samantha L Hider40 Anne M Hinks40 Sally L John40

Catherine Potter40 Alan J Silman40 Deborah P M Symmons40 Wendy Thomson40 amp Jane

Worthington40

Type 1 Diabetes

David G Clayton2 David B Dunger241 Sarah Nutland2 Helen E Stevens2 Neil M Walker2 Barry

Widmer241 amp John A Todd2

Type 2 Diabetes

Timothy M Frayling4243 Rachel M Freathy4243 Hana Lango4243 John R B Perry4243 Beverley M

Shields43 Michael N Weedon4243 Andrew T Hattersley (Exeter)4243 Graham A Hitman (London)44

Mark Walker (Newcastle)45 Kate S Elliott37 Christopher J Groves7 Cecilia M Lindgren37 Nigel W

Rayner37 Nicholas J Timpson346 Eleftheria Zeggini37 amp Mark I McCarthy (Oxford)37

Tuberculosis

Melanie Newport47 Giorgio Sirugo (Gambia)47 Emily Lyons3 Fredrik Vannberg3 amp Adrian V S Hill

(Oxford)3


Ankylosing Spondylitis

Linda A Bradbury48 Claire Farrar49 Jennifer J Pointon48 Paul Wordsworth49 amp Matthew A

Brown4849

Autoimmune Thyroid Disease

Jayne A Franklyn50 Joanne M Heward50 Matthew J Simmonds50 amp Stephen C L Gough50

Breast Cancer

Sheila Seal51 Breast Cancer Susceptibility Collaboration (UK)55 Michael R Stratton5152 amp Nazneen

Rahman51

Multiple Sclerosis

Maria Ban53 An Goris53 Stephen J Sawcer53 amp Alastair Compston53

Gambian Controls

David Conway47 Muminatou Jallow47 Melanie Newport47 Giorgio Sirugo (Gambia)47 Kirk A

Rockett3 amp Dominic P Kwiatkowski (Oxford)35

DNA Genotyping Data QC and Informatics

Suzannah J Bumpstead5 Amy Chaney5 Kate Downes25 Mohammed J R Ghori5 Rhian Gwilliam5

Sarah E Hunt5 Michael Inouye5 Andrew Keniry5 Emma King5 Ralph McGinnis5 Simon Potter5 Rathi

Ravindrarajah5 Pamela Whittaker5 Claire Widden5 David Withers5 Panos Deloukas (Wellcome

Trust Sanger Institute Hinxton)6 Hin-Tak Leung2 Sarah Nutland2 Helen E Stevens2 Neil M Walker2

amp John A Todd (Cambridge)2

Statistics

Doug Easton12 David G Clayton (Cambridge)2 Paul R Burton1 Martin D Tobin (Leicester)1 Jeffrey

C Barrett3 David Evans3 Andrew P Morris3 Lon R Cardon (Oxford)3 Niall J Cardin11 Dan

Davison11 Teresa Ferreira11 Joanne Pereira-Gale11 Ingileif B Hallgrimsdoacutettir11 Bryan N Howie11

Jonathan L Marchini11 Chris C A Spencer11 Zhan Su11 Yik Ying Teo311 Damjan Vukcevic11 amp Peter

Donnelly (Oxford)11

Primary Investigators

David Bentley554 Matthew A Brown4849 Lon R Cardon3 Mark Caulfield38 David G Clayton2 Alistair

Compston53 Nick Craddock23 Panos Deloukas5 Peter Donnelly11 Martin Farrall39 Stephen C L

Gough50 Alistair S Hall26 Andrew T Hattersley4243 Adrian V S Hill3 Dominic P Kwiatkowski35

Christopher G Mathew29 Mark I McCarthy37 Willem H Ouwehand89 Miles Parkes27 Marcus

Pembrey1820 Nazneen Rahman51 Nilesh J Samani10 Michael R Stratton5152 John A Todd2 amp Jane

Worthington40


1 Genetic Epidemiology Group Department of Health Sciences University of Leicester Adrian Building University Road Leicester LE1 7RH UK

2 Juvenile Diabetes Research FoundationWellcome Trust Diabetes and Inflammation Laboratory Department of Medical Genetics Cambridge Institute for Medical Research University of Cambridge Wellcome TrustMRC Building Cambridge CB2 0XY UK

3 Wellcome Trust Centre for Human Genetics University of Oxford Roosevelt Drive Oxford OX3 7BN UK

4 Department of Psychological Medicine Henry Wellcome Building School of Medicine Cardiff University Heath Park Cardiff CF14 4XN UK

5 The Wellcome Trust Sanger Institute Wellcome Trust Genome Campus Hinxton Cambridge CB10 1SA UK

6 The Wellcome Trust Gibbs Building 215 Euston Road London NW1 2BE UK 7 Oxford Centre for Diabetes Endocrinology and Medicine University of Oxford Churchill

Hospital Oxford OX3 7LJ UK 8 Department of Haematology University of Cambridge Long Road Cambridge CB2 2PT UK 9 National Health Service Blood and Transplant Cambridge Centre Long Road Cambridge CB2

2PT UK 10 Department of Cardiovascular Sciences University of Leicester Glenfield Hospital Groby

Road Leicester LE3 9QP UK 11 Department of Statistics University of Oxford 1 South Parks Road Oxford OX1 3TG UK 12 Cancer Research UK Genetic Epidemiology Unit Strangeways Research Laboratory Worts

Causeway Cambridge CB1 8RN UK 13 National Health Service Blood and Transplant Sheffield Centre Longley Lane Sheffield S5

7JN UK 14 National Health Service Blood and Transplant Brentwood Centre Crescent Drive

Brentwood CM15 8DP UK 15 The Welsh Blood Service Ely Valley Road Talbot Green Pontyclun CF72 9WB UK 16 The Scottish National Blood Transfusion Service Ellens Glen Road Edinburgh EH17 7QT UK 17 National Health Service Blood and Transplant Southampton Centre Coxford Road

Southampton SO16 5AF UK 18 Avon Longitudinal Study of Parents and Children University of Bristol 24 Tyndall Avenue

Bristol BS8 1TQ UK 19 Division of Community Health Services St Georges University of London Cranmer Terrace

London SW17 0RE UK 20 Institute of Child Health University College London 30 Guilford Street London WC1N 1EH

UK 21 University of Aberdeen Institute of Medical Sciences Foresterhill Aberdeen AB25 2ZD UK 22 Department of Psychiatry Division of Neuroscience Birmingham University Birmingham

B15 2QZ UK 23 Department of Psychological Medicine Henry Wellcome Building School of Medicine

Cardiff University Heath Park Cardiff CF14 4XN UK 24 SGDP The Institute of Psychiatry Kings College London De Crespigny Park Denmark Hill

London SE5 8AF UK 25 School of Neurology Neurobiology and Psychiatry Royal Victoria Infirmary Queen Victoria

Road Newcastle upon Tyne NE1 4LP UK 26 LIGHT and LIMM Research Institutes Faculty of Medicine and Health University of Leeds

Leeds LS1 3EX UK 27 IBD Research Group Addenbrookes Hospital University of Cambridge Cambridge CB2 2QQ

UK 28 Gastrointestinal Unit School of Molecular and Clinical Medicine University of Edinburgh

Western General Hospital Edinburgh EH4 2XU UK


29 Department of Medical amp Molecular Genetics Kings College London School of Medicine 8th Floor Guys Tower Guys Hospital London SE1 9RT UK

30 Institute for Digestive Diseases University College London Hospitals Trust London NW1 2BU UK

31 Department of Gastroenterology Guys and St Thomas NHS Foundation Trust London SE1 7EH UK

32 Department of Gastroenterology amp Hepatology University of Newcastle upon Tyne Royal Victoria Infirmary Newcastle upon Tyne NE1 4LP UK

33 Gastroenterology Unit Radcliffe Infirmary University of Oxford Oxford OX2 6HE UK 34 Medicine and Therapeutics Aberdeen Royal Infirmary Foresterhill Aberdeen Grampian

AB9 2ZB UK 35 Clinical Pharmacology Unit and the Diabetes and Inflammation Laboratory University of

Cambridge Addenbrookes Hospital Hills Road Cambridge CB2 2QQ UK 36 Centre National de Genotypage 2 Rue Gaston Cremieux Evry Paris 91057 France 37 BHF Glasgow Cardiovascular Research Centre University of Glasgow 126 University Place

Glasgow G12 8TA UK 38 Clinical Pharmacology and Barts and The London Genome Centre William Harvey Research

Institute Barts and The London Queen Marys School of Medicine Charterhouse Square London EC1M 6BQ UK

39 Cardiovascular Medicine University of Oxford Wellcome Trust Centre for Human Genetics Roosevelt Drive Oxford OX3 7BN UK

40 arc Epidemiology Research Unit University of Manchester Stopford Building Oxford Rd Manchester M13 9PT UK

41 Department of Paediatrics University of Cambridge Addenbrookes Hospital Cambridge CB2 2QQ UK

42 Genetics of Complex Traits Institute of Biomedical and Clinical Science Peninsula Medical School Magdalen Road Exeter EX1 2LU UK

43 Diabetes Genetics Institute of Biomedical and Clinical Science Peninsula Medical School Barrack Road Exeter EX2 5DU UK

44 Centre for Diabetes and Metabolic Medicine Barts and The London Royal London Hospital Whitechapel London E1 1BB UK

45 Diabetes Research Group School of Clinical Medical Sciences Newcastle University Framlington Place Newcastle upon Tyne NE2 4HH UK

46 The MRC Centre for Causal Analyses in Translational Epidemiology Bristol University Canynge Hall Whiteladies Rd Bristol BS2 8PR UK

47 MRC Laboratories Fajara The Gambia 48 Diamantina Institute for Cancer Immunology and Metabolic Medicine Princess Alexandra

Hospital University of Queensland Woolloongabba Qld 4102 Australia 49 Botnar Research Centre University of Oxford Headington Oxford OX3 7BN UK 50 Department of Medicine Division of Medical Sciences Institute of Biomedical Research

University of Birmingham Edgbaston Birmingham B15 2TT UK 51 Section of Cancer Genetics Institute of Cancer Research 15 Cotswold Road Sutton SM2

5NG UK 52 Cancer Genome Project The Wellcome Trust Sanger Institute Wellcome Trust Genome

Campus Hinxton Cambridge CB10 1SA UK 53 Department of Clinical Neurosciences University of Cambridge Addenbrookes Hospital

Hills Road Cambridge CB2 2QQ UK


Start 196524

Chromosome Y 1735

Mitochondrial 1

Non-polymorphic (all samples) 12715

Low cluster separation (lt 04) 12510

Low call frequency(lt 098) 2243

Illumina default exclusions 936

Duplicate SNPs 835

Remaining for analysis 165549

Group

SNP loss

Final Call Frequency

(lt099) HWE MAF

UK 2468 680 36543 125858

US 10484 299 34769 119997

SE-E 3851 248 36788 124662

SE-U 3229 156 38037 124127

NL 3321 233 37070 124925

ES 4491 51 36169 124838

Included in Study (passed QC in at least 2 studies) 129464

Supplementary Table 2 Summary of SNPs failing Immunochip quality control metrics








PBC

4 rs12506688 26104113 RBPJ A 373E-10 11337 251E-10 11571 416E-02 10652 RA T1D



9 rs2812378 34710260 CCL21 G 131E-08 11167 723E-10 11473 140E-02 10756 RA

20 rs6032662 44734310 CD40 G 172E-05 09104 137E-09 08564 710E-01 10123 RA MS


2 rs10209110 100672692 AFF3 A 113E-08 08996 679E-08 0891 001231 09317 RA T1D



5 rs39984 102597292 GIN1 A 929E-08 08792 304E-06 08756 132E-04 08674 RA SLE



22 rs3218251 37545505 IL2RB A 582E-06 10987 191E-07 11325 215E-01 10402 RAT1D




2 rs6546146 65556324 SPRED2 A 191E-05 09205 798E-07 08952 505E-01 09805 RA




8 rs4840565 11345545 BLK G 388E-06 10987 346E-04 10877 101E-04 11275 SLE RA

1 rs798000 117280696 CD2 G 892E-05 10802 619E-06 11081 443E-01 10234 RA MS

12 rs10683701 58092089 KIF5A - 439E-05 09221 231E-05 09072 403E-01 09751 RAMS

1 rs16843807 198745722 PTPRC C 110E-04 08905 248E-05 0863 638E-01 09787 RA








15 rs8026898 69991417 TLE3 A 222E-09 11327 137E-10 11662 370E-03 10969 BD

15 rs8043085 38828140 RASGRP1 A 163E-07 11193 140E-10 11713 372E-01 10303 T1D

1 rs2240336 17674402 PADI4 A 364E-08 09003 591E-09 08794 283E-02 09381 RA





7 rs75351767 37427351 ELMO1 G 294E-07 11604 385E-05 11473 595E-05 11917


6 rs72928038 90976768 BACH2 A 823E-07 11282 112E-04 11156 216E-03 11207 T1D CD

3 rs1875463 143165502 SLC9A9 A 151E-06 08996 288E-04 09119 475E-05 08709

10 rs12764378 63800004 ARID5B A 181E-05 10994 164E-06 11292 696E-01 10135


14 rs911263 68753593 ACTN1 G 459E-04 09302 228E-06 08924 833E-01 09934 T1D

10 rs3802604 8102272 GATA3 G 507E-05 10813 368E-06 11085 217E-01 10372


13 rs7993214 40350912 COG6 A 102E-04 09263 455E-06 09005 432E-01 09768


13 rs17230016 82338338 SPRY2 G 961E-06 08838 178E-04 0886 144E-03 08709






REL 2 61136129 rs13031237 140E-09 61136129 rs13031237 126E-11

SPRED2 2 65597671 rs11673987 349E-08 65598241 rs1858036 748E-10

AFF3 2 100806514 rs6712515 282E-11 100806514 rs6712515 200E-11

STAT4 2 191969879 rs10181656 234E-13 191921874 rs11893432 153E-11

CD28|CTLA4 2 204738919 rs3087243 748E-11 204738919 rs3087243 388E-11

RBPJ 4 26086569 rs17630466 567E-13 26104113 rs12506688 600E-13

ANKRD55 5 55440730 rs71624119 568E-20 55440730 rs71624119 120E-11

GIN1 5 102608924 rs2561477 652E-10 102608924 rs2561477 856E-08

TNFAIP3 6 138006504 rs6920220 424E-15 138006504 rs6920220 355E-18

TAGAP 6 159489791 rs212389 299E-05 159489791 rs212389 911E-09

CCR6 6 167540842 rs1571878 229E-08 167540842 rs1571878 123E-12

IRF5 7 128580680 rs3807306 712E-10 128580680 rs3807306 475E-10

CCL21 9 34710260 rs2812378 850E-09 34710260 rs2812378 126E-09

TRAF1 9 123683569 rs2269060 371E-07 123683569 rs2269060 173E-08

IL2RA 10 6108340 rs10795791 111E-09 6108340 rs10795791 119E-09

DDX6 11 118611781 rs10892279 295E-08 118611781 rs10892279 134E-10


POU3F1 1 38616871 rs883220 119E-07 38616871 rs883220 209E-08

IL6R 1 154426970 rs2228145 130E-08 154426970 rs2228145 158E-07

GATA3 10 8095340 rs2275806 738E-08 8095340 rs2275806 458E-08

ARID5B 10 63800004 rs12764378 100E-08 63800004 rs12764378 445E-10

CD5 11 60909581 rs595158 335E-08 60909581 rs595158 556E-06

RASGRP1 15 38828140 rs8043085 176E-08 38828140 rs8043085 482E-11

TLE3 15 69991417 rs8026898 603E-11 69991417 rs8026898 652E-12

IRF8 16 86019087 rs13330176 168E-07 86019087 rs13330176 530E-09

IKZF3 17 38062196 rs2305480 420E-09 38040763 rs2872507 279E-09

TYK2 19 10463118 rs34536443 269E-13 10463118 rs34536443 224E-14

RCAN1 21 35911599 rs2834512 431E-07 35911599 rs2834512 306E-08

RUNX1 21 36715761 rs9979383 503E-10 36715761 rs9979383 369E-08





(OR) META ACPA-



META OR of OR ( OR)


1 rs2476601 114179091 PTPN22 923E-78 179 260E-04 118 244E-19 149

6 rs59466457 167457744 CCR6 477E-10 114 684E-01 099 100E-06 116

20 rs6032662 44167717 CD40 422E-09 086 831E-01 101 596E-06 085

15 rs8043085 36615432 RASGRP1 345E-10 117 363E-01 103 213E-04 114

6 rs629326 159416701 TAGAP 259E-06 090 717E-01 101 236E-04 089

11 rs4938573 118247052 DDX6 484E-07 087 596E-01 098 146E-03 089

15 rs77397211 36757788 RASGRP1 110E-03 115 524E-01 096 153E-03 121

2 rs34695944 60978354 REL 176E-08 113 359E-01 103 181E-03 110

1 rs2843401 2517993 MMEL1 800E-09 087 541E-01 098 188E-03 090

6 rs58721818 138285432 TNFAIP3 594E-12 146 899E-02 114 215E-03 127

2 rs6546146 65409828 SPRED2 603E-07 089 508E-01 098 220E-03 091

19 rs34536443 10324118 TYK2 303E-14 062 750E-03 082 295E-03 077

16 rs13330176 84576588 IRF8 872E-08 114 726E-01 101 340E-03 111

10 rs12722508 6128749 IL2RA 201E-05 085 891E-01 101 367E-03 086

1 rs798000 117082219 CD2 431E-06 111 469E-01 102 727E-03 109

10 rs12764378 63470010 ARID5B 900E-07 113 656E-01 102 881E-03 110

2 rs11571302 204451179 CTLA4CD28 456E-08 089 105E-01 096 890E-03 092

6 rs6920220 138048197 TNFAIP3 309E-13 120 220E-02 108 986E-03 110

4 rs932036 25699960 RBPJ 355E-10 116 176E-02 108 178E-02 108

17 rs2872507 35294289 GSDML 131E-06 111 239E-01 103 276E-02 107

9 rs2812378 34700260 CCL21 518E-10 115 117E-02 108 356E-02 107

21 rs2834512 34833469 RCAN1 293E-04 088 507E-01 097 441E-02 091

17 rs12936409 35297175 GSDML 771E-07 111 113E-01 105 452E-02 106


5 rs71624119 55476487 ANKRD55 171E-11 084 623E-12 079 825E-02 107


8 rs4840565 11382954 BLK 343E-04 109 853E-05 113 332E-01 097

21 rs9979383 35637631 RUNX1 315E-05 091 990E-05 089 554E-01 102

5 rs39984 102625191 GIN1 383E-06 088 165E-04 087 761E-01 101

1 rs2014863 197076224 PTPRC 874E-04 108 835E-04 110 369E-01 097

2 rs932169 191637523 STAT4 239E-02 109 116E-03 118 120E-01 092

19 rs3176767 10310751 ICAM3 271E-05 111 191E-03 111 859E-01 101

4 rs78560100 123260921 IL2_21 117E-03 114 214E-03 118 641E-01 097

2 rs13426947 191641499 STAT4 494E-09 117 262E-03 111 170E-01 105

11 rs595158 60666157 CD5 176E-05 110 597E-03 108 642E-01 101

3 rs35677470 58158676 DNASE1L3 150E-06 121 928E-03 115 516E-01 104





1 2528133 rs2843401 709E-06 TNFRSF14

1 17674537 rs2240335 404E-02 PADI4

1 38616871 rs883220 967E-01 POU3F1

1 114377568 rs2476601 287E-05 PTPN22

1 117263138 rs11586238 369E-10 CD2

1 154426970 rs2228145 305E-05 IL6R

1 161467042 rs12746613 433E-06 FCGR2B

1 167411384 rs864537 220E-11 CD247

1 198700442 rs10919563 125E-10 PTPRC

2 61136129 rs13031237 218E-06 REL

2 65595586 rs934734 144E-01 SPRED2

2 100806940 rs11676922 537E-01 AFF3

2 191935804 rs10168266 961E-09 STAT4

2 204610396 rs1980422 277E-12 CD28

2 204738919 rs3087243 142E-11 ICOS

3 58556841 rs13315591 895E-01 DNASE1L3

4 26104113 rs12506688 739E-01 RBPJ

4 123509421 rs6822844 432E-09 IL2

5 55438580 rs6859219 100E+00 ANKRD55

5 102608924 rs2561477 936E-01 GIN1

6 106568034 rs548234 180E-04 PRDM1

6 138002637 rs10499194 212E-04 TNFAIP3

6 159482521 rs394581 162E-05 TAGAP

6 167540842 rs1571878 426E-07 CCR6

7 128594183 rs10488631 326E-04 IRF5

8 11343973 rs2736340 259E-02 BLK

9 34743681 rs951005 960E-06 CCL21

9 123640500 rs1953126 208E-06 TRAF1

10 6099045 rs2104286 441E-10 IL2RA

10 6393260 rs4750316 422E-08 PRKCQ

10 8095340 rs2275806 726E-05 GATA3

10 63800004 rs12764378 884E-01 ARID5B

11 36525293 rs540386 671E-11 RAG1

11 60909581 rs595158 399E-11 CD5

11 118611781 rs10892279 919E-01 DDX6

12 57968715 rs1678542 658E-01 B4GALNT1

15 38828140 rs8043085 682E-08 RASGRP1

15 69991417 rs8026898 943E-01 KIF23

16 86019087 rs13330176 300E-07 IRF8

17 38040763 rs2872507 247E-05 IKZF3

19 10295433 rs4804493 751E-01 DNMT1


20 44734310 rs6032662 438E-10 CD40

21 35911599 rs2834512 197E-01 RCAN1

21 36715761 rs9979383 914E-02 RUNX1

21 43836186 rs11203203 106E-01 UBASH3A

22 21982892 rs2298428 964E-01 YDJC

22 37544810 rs3218253 100E-08 IL2RB





1-SNP model

Haplotypic risk

SNP alleles

(Mm)


(Mm)



AG 072 126

GG 023 143

GA 00002 -


CG 006 117

AA 023 118

AG 001 139

2p16-p15


AG 058 12

GG 038 136

GA 0005 -


AT 024 115

CA 006 120

AA 0 -


AG 021 118

GA 002 137

AA 002 155


CC 009 085

GA 004 062

GC 0 -



Chr POS Gene region

Lead SNP Low MAF

SNP

MAF

UNAFF

MAF

AFF

P OR r2

to lead

Location REG POT7X

CONS 17WA

Y


2 61391558 REL rs17008218 005 004 439E-05 083 1 INTRONIC 000 008

2 61581489 REL rs17009924 005 004 947E-05 084 092 INTRONIC 000 000

















GWAS IMMUNOCHIP


P OR

rs13315591a PXK 3 009 46x10-8 129 rs35677470 008 17 X 10-07 119 028 103 027 058

rs10488631 IRF5 7 011 42x10-11 119 rs3807306 049 19 X 10-07 089 18 X 10-05 11 02 1

rs934734 SPRED2 2 049 53x10-10 113 rs6546146 038 80 X 10-07 09 30 X 10-04 107 053 095

rs3761847 TRAF1 9 043 21x10-7 113 rs10739580 033 17 X 10-06 112 17 X 10-04 107 074 1

rs2104286 IL2RA 10 027 2x10-3 092 rs10795791 04 30 X 10-06 109 10 X 10-04 091 025 1

rs11586238 CD2 1 024 1x10-5 113 rs798000 034 62 X 10-06 111 30 X 10-03 107 033 072

rs10919563 PTPRC 1 013 2x10-4 088 rs2014863 036 21 X 10-05 109 77 X 10-04 091 007 1

rs1678542 KIF5A 12 038 2x10-4 091 rs10683701 033 23 X 10-05 09 10 X 10-03 093 027 058

rs548234 PRDM1 6 033 97x10-5 11 rs6911690 012 12 X 10-04 087 002 104 01 1

rs6822844 IL2-IL21 4 018 7x10-4 09 rs78560100 007 58 X 10-04 113 001 094 002 1

rs540386b TRAF6 11 014 3x10-4 088 rs570676 038 21 X 10-03 093 007 095 018 1




Region size


Region size


LD SNPS (ns)

r2gt09




PTPN22 1p13 113863087-

114527968

665kb

rs2476601b 114303808-114377568



ANKRD55 5q11 55414956-

55447909

33kb

rs71624119a 55440730-55442249


TNFAIP3 6q23 137896596-

138125335

229kb

rs6920220b 137959235-138006504

4727kb 761 (0) 9 (0) 18185kb 5 of TNFAIP3

TNFAIP3 6q23 137896596-

138125335

229kb

rs58721818g 138178293-

138243739

6545kb 835 (38) 7 (0) TNFAIP3

RBPJ 4p15 26028805-

26134465

106kb

rs932036a 26085480-26128710

4323kb 486 (0) 25 (0) 3637kb 5 of RBPJ

CCR6 6q27 167355854-

167547954

192kb

rs59466457b 167526096-

167540842

1475kb 234 (0) 6 (0) Intron 1 of CCR6

STAT4 2q32 191873553-

192007734

134kb

rs13426947a 191900449-191935804


STAT4 2q32 191873553- 134kb rs932169e 191929278-191929278



192007734

CCL21 9p13 34649442-

34974974

325kb rs2812378b 34707373-34710338

297kb 41 (4) 3 (0) CCL21

CD40 20q13 44594228-

44784336

190kb

rs6032662b 44730245-44747947


MMEL1 1p36 2406888-

2785671

378kb

rs2843401b 2516781-2709164

19238kb

4571 (73)

85 (1)


AFF3 2q11 100544954-

101038647

493kb

rs10209110a 100640432-100730111


REL 2p16 60914729-

61864047

949kb

rs34695944b 61072664-61164331

9167kb 876 (18) 14 (0) Complete REL

REL 2p16 60914729-

61864047

949kb

rs78404002g 61466603-61776131

30953kb

3579 (24)

5 (0)


USP34 SNORA70B XPO1

31596kb 3 of REL CTLA4 2q33 204678417-

204816382

138kb

rs11571302b 204738919-204745003


GIN1 5q21 102098582-

102711659

613kb

rs39984a 102595778-102625335

2956kb

385 (7)

40 (0)


13992kb 5of GIN1

PXK 3p14 58154177-

58549297

395kb

rs35677470a 58181499-58183636


13497kb 5 of PXK

IRF5 7q32 128549568- 228kb rs3807306b 128580680-128580680



128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884


SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300


TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485


CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)


CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515



PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40
























































PBC

4 rs12506688 26104113 RBPJ A 373E-10 11337 251E-10 11571 416E-02 10652 RA T1D



9 rs2812378 34710260 CCL21 G 131E-08 11167 723E-10 11473 140E-02 10756 RA

20 rs6032662 44734310 CD40 G 172E-05 09104 137E-09 08564 710E-01 10123 RA MS


2 rs10209110 100672692 AFF3 A 113E-08 08996 679E-08 0891 001231 09317 RA T1D



5 rs39984 102597292 GIN1 A 929E-08 08792 304E-06 08756 132E-04 08674 RA SLE



22 rs3218251 37545505 IL2RB A 582E-06 10987 191E-07 11325 215E-01 10402 RAT1D




2 rs6546146 65556324 SPRED2 A 191E-05 09205 798E-07 08952 505E-01 09805 RA




8 rs4840565 11345545 BLK G 388E-06 10987 346E-04 10877 101E-04 11275 SLE RA

1 rs798000 117280696 CD2 G 892E-05 10802 619E-06 11081 443E-01 10234 RA MS

12 rs10683701 58092089 KIF5A - 439E-05 09221 231E-05 09072 403E-01 09751 RAMS

1 rs16843807 198745722 PTPRC C 110E-04 08905 248E-05 0863 638E-01 09787 RA








15 rs8026898 69991417 TLE3 A 222E-09 11327 137E-10 11662 370E-03 10969 BD

15 rs8043085 38828140 RASGRP1 A 163E-07 11193 140E-10 11713 372E-01 10303 T1D

1 rs2240336 17674402 PADI4 A 364E-08 09003 591E-09 08794 283E-02 09381 RA





7 rs75351767 37427351 ELMO1 G 294E-07 11604 385E-05 11473 595E-05 11917


6 rs72928038 90976768 BACH2 A 823E-07 11282 112E-04 11156 216E-03 11207 T1D CD

3 rs1875463 143165502 SLC9A9 A 151E-06 08996 288E-04 09119 475E-05 08709

10 rs12764378 63800004 ARID5B A 181E-05 10994 164E-06 11292 696E-01 10135


14 rs911263 68753593 ACTN1 G 459E-04 09302 228E-06 08924 833E-01 09934 T1D

10 rs3802604 8102272 GATA3 G 507E-05 10813 368E-06 11085 217E-01 10372


13 rs7993214 40350912 COG6 A 102E-04 09263 455E-06 09005 432E-01 09768


13 rs17230016 82338338 SPRY2 G 961E-06 08838 178E-04 0886 144E-03 08709






REL 2 61136129 rs13031237 140E-09 61136129 rs13031237 126E-11

SPRED2 2 65597671 rs11673987 349E-08 65598241 rs1858036 748E-10

AFF3 2 100806514 rs6712515 282E-11 100806514 rs6712515 200E-11

STAT4 2 191969879 rs10181656 234E-13 191921874 rs11893432 153E-11

CD28|CTLA4 2 204738919 rs3087243 748E-11 204738919 rs3087243 388E-11

RBPJ 4 26086569 rs17630466 567E-13 26104113 rs12506688 600E-13

ANKRD55 5 55440730 rs71624119 568E-20 55440730 rs71624119 120E-11

GIN1 5 102608924 rs2561477 652E-10 102608924 rs2561477 856E-08

TNFAIP3 6 138006504 rs6920220 424E-15 138006504 rs6920220 355E-18

TAGAP 6 159489791 rs212389 299E-05 159489791 rs212389 911E-09

CCR6 6 167540842 rs1571878 229E-08 167540842 rs1571878 123E-12

IRF5 7 128580680 rs3807306 712E-10 128580680 rs3807306 475E-10

CCL21 9 34710260 rs2812378 850E-09 34710260 rs2812378 126E-09

TRAF1 9 123683569 rs2269060 371E-07 123683569 rs2269060 173E-08

IL2RA 10 6108340 rs10795791 111E-09 6108340 rs10795791 119E-09

DDX6 11 118611781 rs10892279 295E-08 118611781 rs10892279 134E-10


POU3F1 1 38616871 rs883220 119E-07 38616871 rs883220 209E-08

IL6R 1 154426970 rs2228145 130E-08 154426970 rs2228145 158E-07

GATA3 10 8095340 rs2275806 738E-08 8095340 rs2275806 458E-08

ARID5B 10 63800004 rs12764378 100E-08 63800004 rs12764378 445E-10

CD5 11 60909581 rs595158 335E-08 60909581 rs595158 556E-06

RASGRP1 15 38828140 rs8043085 176E-08 38828140 rs8043085 482E-11

TLE3 15 69991417 rs8026898 603E-11 69991417 rs8026898 652E-12

IRF8 16 86019087 rs13330176 168E-07 86019087 rs13330176 530E-09

IKZF3 17 38062196 rs2305480 420E-09 38040763 rs2872507 279E-09

TYK2 19 10463118 rs34536443 269E-13 10463118 rs34536443 224E-14

RCAN1 21 35911599 rs2834512 431E-07 35911599 rs2834512 306E-08

RUNX1 21 36715761 rs9979383 503E-10 36715761 rs9979383 369E-08





(OR) META ACPA-



META OR of OR ( OR)


1 rs2476601 114179091 PTPN22 923E-78 179 260E-04 118 244E-19 149

6 rs59466457 167457744 CCR6 477E-10 114 684E-01 099 100E-06 116

20 rs6032662 44167717 CD40 422E-09 086 831E-01 101 596E-06 085

15 rs8043085 36615432 RASGRP1 345E-10 117 363E-01 103 213E-04 114

6 rs629326 159416701 TAGAP 259E-06 090 717E-01 101 236E-04 089

11 rs4938573 118247052 DDX6 484E-07 087 596E-01 098 146E-03 089

15 rs77397211 36757788 RASGRP1 110E-03 115 524E-01 096 153E-03 121

2 rs34695944 60978354 REL 176E-08 113 359E-01 103 181E-03 110

1 rs2843401 2517993 MMEL1 800E-09 087 541E-01 098 188E-03 090

6 rs58721818 138285432 TNFAIP3 594E-12 146 899E-02 114 215E-03 127

2 rs6546146 65409828 SPRED2 603E-07 089 508E-01 098 220E-03 091

19 rs34536443 10324118 TYK2 303E-14 062 750E-03 082 295E-03 077

16 rs13330176 84576588 IRF8 872E-08 114 726E-01 101 340E-03 111

10 rs12722508 6128749 IL2RA 201E-05 085 891E-01 101 367E-03 086

1 rs798000 117082219 CD2 431E-06 111 469E-01 102 727E-03 109

10 rs12764378 63470010 ARID5B 900E-07 113 656E-01 102 881E-03 110

2 rs11571302 204451179 CTLA4CD28 456E-08 089 105E-01 096 890E-03 092

6 rs6920220 138048197 TNFAIP3 309E-13 120 220E-02 108 986E-03 110

4 rs932036 25699960 RBPJ 355E-10 116 176E-02 108 178E-02 108

17 rs2872507 35294289 GSDML 131E-06 111 239E-01 103 276E-02 107

9 rs2812378 34700260 CCL21 518E-10 115 117E-02 108 356E-02 107

21 rs2834512 34833469 RCAN1 293E-04 088 507E-01 097 441E-02 091

17 rs12936409 35297175 GSDML 771E-07 111 113E-01 105 452E-02 106


5 rs71624119 55476487 ANKRD55 171E-11 084 623E-12 079 825E-02 107


8 rs4840565 11382954 BLK 343E-04 109 853E-05 113 332E-01 097

21 rs9979383 35637631 RUNX1 315E-05 091 990E-05 089 554E-01 102

5 rs39984 102625191 GIN1 383E-06 088 165E-04 087 761E-01 101

1 rs2014863 197076224 PTPRC 874E-04 108 835E-04 110 369E-01 097

2 rs932169 191637523 STAT4 239E-02 109 116E-03 118 120E-01 092

19 rs3176767 10310751 ICAM3 271E-05 111 191E-03 111 859E-01 101

4 rs78560100 123260921 IL2_21 117E-03 114 214E-03 118 641E-01 097

2 rs13426947 191641499 STAT4 494E-09 117 262E-03 111 170E-01 105

11 rs595158 60666157 CD5 176E-05 110 597E-03 108 642E-01 101

3 rs35677470 58158676 DNASE1L3 150E-06 121 928E-03 115 516E-01 104





1 2528133 rs2843401 709E-06 TNFRSF14

1 17674537 rs2240335 404E-02 PADI4

1 38616871 rs883220 967E-01 POU3F1

1 114377568 rs2476601 287E-05 PTPN22

1 117263138 rs11586238 369E-10 CD2

1 154426970 rs2228145 305E-05 IL6R

1 161467042 rs12746613 433E-06 FCGR2B

1 167411384 rs864537 220E-11 CD247

1 198700442 rs10919563 125E-10 PTPRC

2 61136129 rs13031237 218E-06 REL

2 65595586 rs934734 144E-01 SPRED2

2 100806940 rs11676922 537E-01 AFF3

2 191935804 rs10168266 961E-09 STAT4

2 204610396 rs1980422 277E-12 CD28

2 204738919 rs3087243 142E-11 ICOS

3 58556841 rs13315591 895E-01 DNASE1L3

4 26104113 rs12506688 739E-01 RBPJ

4 123509421 rs6822844 432E-09 IL2

5 55438580 rs6859219 100E+00 ANKRD55

5 102608924 rs2561477 936E-01 GIN1

6 106568034 rs548234 180E-04 PRDM1

6 138002637 rs10499194 212E-04 TNFAIP3

6 159482521 rs394581 162E-05 TAGAP

6 167540842 rs1571878 426E-07 CCR6

7 128594183 rs10488631 326E-04 IRF5

8 11343973 rs2736340 259E-02 BLK

9 34743681 rs951005 960E-06 CCL21

9 123640500 rs1953126 208E-06 TRAF1

10 6099045 rs2104286 441E-10 IL2RA

10 6393260 rs4750316 422E-08 PRKCQ

10 8095340 rs2275806 726E-05 GATA3

10 63800004 rs12764378 884E-01 ARID5B

11 36525293 rs540386 671E-11 RAG1

11 60909581 rs595158 399E-11 CD5

11 118611781 rs10892279 919E-01 DDX6

12 57968715 rs1678542 658E-01 B4GALNT1

15 38828140 rs8043085 682E-08 RASGRP1

15 69991417 rs8026898 943E-01 KIF23

16 86019087 rs13330176 300E-07 IRF8

17 38040763 rs2872507 247E-05 IKZF3

19 10295433 rs4804493 751E-01 DNMT1


20 44734310 rs6032662 438E-10 CD40

21 35911599 rs2834512 197E-01 RCAN1

21 36715761 rs9979383 914E-02 RUNX1

21 43836186 rs11203203 106E-01 UBASH3A

22 21982892 rs2298428 964E-01 YDJC

22 37544810 rs3218253 100E-08 IL2RB





1-SNP model

Haplotypic risk

SNP alleles

(Mm)


(Mm)



AG 072 126

GG 023 143

GA 00002 -


CG 006 117

AA 023 118

AG 001 139

2p16-p15


AG 058 12

GG 038 136

GA 0005 -


AT 024 115

CA 006 120

AA 0 -


AG 021 118

GA 002 137

AA 002 155


CC 009 085

GA 004 062

GC 0 -



Chr POS Gene region

Lead SNP Low MAF

SNP

MAF

UNAFF

MAF

AFF

P OR r2

to lead

Location REG POT7X

CONS 17WA

Y


2 61391558 REL rs17008218 005 004 439E-05 083 1 INTRONIC 000 008

2 61581489 REL rs17009924 005 004 947E-05 084 092 INTRONIC 000 000

















GWAS IMMUNOCHIP


P OR

rs13315591a PXK 3 009 46x10-8 129 rs35677470 008 17 X 10-07 119 028 103 027 058

rs10488631 IRF5 7 011 42x10-11 119 rs3807306 049 19 X 10-07 089 18 X 10-05 11 02 1

rs934734 SPRED2 2 049 53x10-10 113 rs6546146 038 80 X 10-07 09 30 X 10-04 107 053 095

rs3761847 TRAF1 9 043 21x10-7 113 rs10739580 033 17 X 10-06 112 17 X 10-04 107 074 1

rs2104286 IL2RA 10 027 2x10-3 092 rs10795791 04 30 X 10-06 109 10 X 10-04 091 025 1

rs11586238 CD2 1 024 1x10-5 113 rs798000 034 62 X 10-06 111 30 X 10-03 107 033 072

rs10919563 PTPRC 1 013 2x10-4 088 rs2014863 036 21 X 10-05 109 77 X 10-04 091 007 1

rs1678542 KIF5A 12 038 2x10-4 091 rs10683701 033 23 X 10-05 09 10 X 10-03 093 027 058

rs548234 PRDM1 6 033 97x10-5 11 rs6911690 012 12 X 10-04 087 002 104 01 1

rs6822844 IL2-IL21 4 018 7x10-4 09 rs78560100 007 58 X 10-04 113 001 094 002 1

rs540386b TRAF6 11 014 3x10-4 088 rs570676 038 21 X 10-03 093 007 095 018 1




Region size


Region size


LD SNPS (ns)

r2gt09




PTPN22 1p13 113863087-

114527968

665kb

rs2476601b 114303808-114377568



ANKRD55 5q11 55414956-

55447909

33kb

rs71624119a 55440730-55442249


TNFAIP3 6q23 137896596-

138125335

229kb

rs6920220b 137959235-138006504

4727kb 761 (0) 9 (0) 18185kb 5 of TNFAIP3

TNFAIP3 6q23 137896596-

138125335

229kb

rs58721818g 138178293-

138243739

6545kb 835 (38) 7 (0) TNFAIP3

RBPJ 4p15 26028805-

26134465

106kb

rs932036a 26085480-26128710

4323kb 486 (0) 25 (0) 3637kb 5 of RBPJ

CCR6 6q27 167355854-

167547954

192kb

rs59466457b 167526096-

167540842

1475kb 234 (0) 6 (0) Intron 1 of CCR6

STAT4 2q32 191873553-

192007734

134kb

rs13426947a 191900449-191935804


STAT4 2q32 191873553- 134kb rs932169e 191929278-191929278



192007734

CCL21 9p13 34649442-

34974974

325kb rs2812378b 34707373-34710338

297kb 41 (4) 3 (0) CCL21

CD40 20q13 44594228-

44784336

190kb

rs6032662b 44730245-44747947


MMEL1 1p36 2406888-

2785671

378kb

rs2843401b 2516781-2709164

19238kb

4571 (73)

85 (1)


AFF3 2q11 100544954-

101038647

493kb

rs10209110a 100640432-100730111


REL 2p16 60914729-

61864047

949kb

rs34695944b 61072664-61164331

9167kb 876 (18) 14 (0) Complete REL

REL 2p16 60914729-

61864047

949kb

rs78404002g 61466603-61776131

30953kb

3579 (24)

5 (0)


USP34 SNORA70B XPO1

31596kb 3 of REL CTLA4 2q33 204678417-

204816382

138kb

rs11571302b 204738919-204745003


GIN1 5q21 102098582-

102711659

613kb

rs39984a 102595778-102625335

2956kb

385 (7)

40 (0)


13992kb 5of GIN1

PXK 3p14 58154177-

58549297

395kb

rs35677470a 58181499-58183636


13497kb 5 of PXK

IRF5 7q32 128549568- 228kb rs3807306b 128580680-128580680



128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884


SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300


TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485


CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)


CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515



PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40



















































2 rs6546146 65556324 SPRED2 A 191E-05 09205 798E-07 08952 505E-01 09805 RA




8 rs4840565 11345545 BLK G 388E-06 10987 346E-04 10877 101E-04 11275 SLE RA

1 rs798000 117280696 CD2 G 892E-05 10802 619E-06 11081 443E-01 10234 RA MS

12 rs10683701 58092089 KIF5A - 439E-05 09221 231E-05 09072 403E-01 09751 RAMS

1 rs16843807 198745722 PTPRC C 110E-04 08905 248E-05 0863 638E-01 09787 RA








15 rs8026898 69991417 TLE3 A 222E-09 11327 137E-10 11662 370E-03 10969 BD

15 rs8043085 38828140 RASGRP1 A 163E-07 11193 140E-10 11713 372E-01 10303 T1D

1 rs2240336 17674402 PADI4 A 364E-08 09003 591E-09 08794 283E-02 09381 RA





7 rs75351767 37427351 ELMO1 G 294E-07 11604 385E-05 11473 595E-05 11917


6 rs72928038 90976768 BACH2 A 823E-07 11282 112E-04 11156 216E-03 11207 T1D CD

3 rs1875463 143165502 SLC9A9 A 151E-06 08996 288E-04 09119 475E-05 08709

10 rs12764378 63800004 ARID5B A 181E-05 10994 164E-06 11292 696E-01 10135


14 rs911263 68753593 ACTN1 G 459E-04 09302 228E-06 08924 833E-01 09934 T1D

10 rs3802604 8102272 GATA3 G 507E-05 10813 368E-06 11085 217E-01 10372


13 rs7993214 40350912 COG6 A 102E-04 09263 455E-06 09005 432E-01 09768


13 rs17230016 82338338 SPRY2 G 961E-06 08838 178E-04 0886 144E-03 08709






REL 2 61136129 rs13031237 140E-09 61136129 rs13031237 126E-11

SPRED2 2 65597671 rs11673987 349E-08 65598241 rs1858036 748E-10

AFF3 2 100806514 rs6712515 282E-11 100806514 rs6712515 200E-11

STAT4 2 191969879 rs10181656 234E-13 191921874 rs11893432 153E-11

CD28|CTLA4 2 204738919 rs3087243 748E-11 204738919 rs3087243 388E-11

RBPJ 4 26086569 rs17630466 567E-13 26104113 rs12506688 600E-13

ANKRD55 5 55440730 rs71624119 568E-20 55440730 rs71624119 120E-11

GIN1 5 102608924 rs2561477 652E-10 102608924 rs2561477 856E-08

TNFAIP3 6 138006504 rs6920220 424E-15 138006504 rs6920220 355E-18

TAGAP 6 159489791 rs212389 299E-05 159489791 rs212389 911E-09

CCR6 6 167540842 rs1571878 229E-08 167540842 rs1571878 123E-12

IRF5 7 128580680 rs3807306 712E-10 128580680 rs3807306 475E-10

CCL21 9 34710260 rs2812378 850E-09 34710260 rs2812378 126E-09

TRAF1 9 123683569 rs2269060 371E-07 123683569 rs2269060 173E-08

IL2RA 10 6108340 rs10795791 111E-09 6108340 rs10795791 119E-09

DDX6 11 118611781 rs10892279 295E-08 118611781 rs10892279 134E-10


POU3F1 1 38616871 rs883220 119E-07 38616871 rs883220 209E-08

IL6R 1 154426970 rs2228145 130E-08 154426970 rs2228145 158E-07

GATA3 10 8095340 rs2275806 738E-08 8095340 rs2275806 458E-08

ARID5B 10 63800004 rs12764378 100E-08 63800004 rs12764378 445E-10

CD5 11 60909581 rs595158 335E-08 60909581 rs595158 556E-06

RASGRP1 15 38828140 rs8043085 176E-08 38828140 rs8043085 482E-11

TLE3 15 69991417 rs8026898 603E-11 69991417 rs8026898 652E-12

IRF8 16 86019087 rs13330176 168E-07 86019087 rs13330176 530E-09

IKZF3 17 38062196 rs2305480 420E-09 38040763 rs2872507 279E-09

TYK2 19 10463118 rs34536443 269E-13 10463118 rs34536443 224E-14

RCAN1 21 35911599 rs2834512 431E-07 35911599 rs2834512 306E-08

RUNX1 21 36715761 rs9979383 503E-10 36715761 rs9979383 369E-08





(OR) META ACPA-



META OR of OR ( OR)


1 rs2476601 114179091 PTPN22 923E-78 179 260E-04 118 244E-19 149

6 rs59466457 167457744 CCR6 477E-10 114 684E-01 099 100E-06 116

20 rs6032662 44167717 CD40 422E-09 086 831E-01 101 596E-06 085

15 rs8043085 36615432 RASGRP1 345E-10 117 363E-01 103 213E-04 114

6 rs629326 159416701 TAGAP 259E-06 090 717E-01 101 236E-04 089

11 rs4938573 118247052 DDX6 484E-07 087 596E-01 098 146E-03 089

15 rs77397211 36757788 RASGRP1 110E-03 115 524E-01 096 153E-03 121

2 rs34695944 60978354 REL 176E-08 113 359E-01 103 181E-03 110

1 rs2843401 2517993 MMEL1 800E-09 087 541E-01 098 188E-03 090

6 rs58721818 138285432 TNFAIP3 594E-12 146 899E-02 114 215E-03 127

2 rs6546146 65409828 SPRED2 603E-07 089 508E-01 098 220E-03 091

19 rs34536443 10324118 TYK2 303E-14 062 750E-03 082 295E-03 077

16 rs13330176 84576588 IRF8 872E-08 114 726E-01 101 340E-03 111

10 rs12722508 6128749 IL2RA 201E-05 085 891E-01 101 367E-03 086

1 rs798000 117082219 CD2 431E-06 111 469E-01 102 727E-03 109

10 rs12764378 63470010 ARID5B 900E-07 113 656E-01 102 881E-03 110

2 rs11571302 204451179 CTLA4CD28 456E-08 089 105E-01 096 890E-03 092

6 rs6920220 138048197 TNFAIP3 309E-13 120 220E-02 108 986E-03 110

4 rs932036 25699960 RBPJ 355E-10 116 176E-02 108 178E-02 108

17 rs2872507 35294289 GSDML 131E-06 111 239E-01 103 276E-02 107

9 rs2812378 34700260 CCL21 518E-10 115 117E-02 108 356E-02 107

21 rs2834512 34833469 RCAN1 293E-04 088 507E-01 097 441E-02 091

17 rs12936409 35297175 GSDML 771E-07 111 113E-01 105 452E-02 106


5 rs71624119 55476487 ANKRD55 171E-11 084 623E-12 079 825E-02 107


8 rs4840565 11382954 BLK 343E-04 109 853E-05 113 332E-01 097

21 rs9979383 35637631 RUNX1 315E-05 091 990E-05 089 554E-01 102

5 rs39984 102625191 GIN1 383E-06 088 165E-04 087 761E-01 101

1 rs2014863 197076224 PTPRC 874E-04 108 835E-04 110 369E-01 097

2 rs932169 191637523 STAT4 239E-02 109 116E-03 118 120E-01 092

19 rs3176767 10310751 ICAM3 271E-05 111 191E-03 111 859E-01 101

4 rs78560100 123260921 IL2_21 117E-03 114 214E-03 118 641E-01 097

2 rs13426947 191641499 STAT4 494E-09 117 262E-03 111 170E-01 105

11 rs595158 60666157 CD5 176E-05 110 597E-03 108 642E-01 101

3 rs35677470 58158676 DNASE1L3 150E-06 121 928E-03 115 516E-01 104





1 2528133 rs2843401 709E-06 TNFRSF14

1 17674537 rs2240335 404E-02 PADI4

1 38616871 rs883220 967E-01 POU3F1

1 114377568 rs2476601 287E-05 PTPN22

1 117263138 rs11586238 369E-10 CD2

1 154426970 rs2228145 305E-05 IL6R

1 161467042 rs12746613 433E-06 FCGR2B

1 167411384 rs864537 220E-11 CD247

1 198700442 rs10919563 125E-10 PTPRC

2 61136129 rs13031237 218E-06 REL

2 65595586 rs934734 144E-01 SPRED2

2 100806940 rs11676922 537E-01 AFF3

2 191935804 rs10168266 961E-09 STAT4

2 204610396 rs1980422 277E-12 CD28

2 204738919 rs3087243 142E-11 ICOS

3 58556841 rs13315591 895E-01 DNASE1L3

4 26104113 rs12506688 739E-01 RBPJ

4 123509421 rs6822844 432E-09 IL2

5 55438580 rs6859219 100E+00 ANKRD55

5 102608924 rs2561477 936E-01 GIN1

6 106568034 rs548234 180E-04 PRDM1

6 138002637 rs10499194 212E-04 TNFAIP3

6 159482521 rs394581 162E-05 TAGAP

6 167540842 rs1571878 426E-07 CCR6

7 128594183 rs10488631 326E-04 IRF5

8 11343973 rs2736340 259E-02 BLK

9 34743681 rs951005 960E-06 CCL21

9 123640500 rs1953126 208E-06 TRAF1

10 6099045 rs2104286 441E-10 IL2RA

10 6393260 rs4750316 422E-08 PRKCQ

10 8095340 rs2275806 726E-05 GATA3

10 63800004 rs12764378 884E-01 ARID5B

11 36525293 rs540386 671E-11 RAG1

11 60909581 rs595158 399E-11 CD5

11 118611781 rs10892279 919E-01 DDX6

12 57968715 rs1678542 658E-01 B4GALNT1

15 38828140 rs8043085 682E-08 RASGRP1

15 69991417 rs8026898 943E-01 KIF23

16 86019087 rs13330176 300E-07 IRF8

17 38040763 rs2872507 247E-05 IKZF3

19 10295433 rs4804493 751E-01 DNMT1


20 44734310 rs6032662 438E-10 CD40

21 35911599 rs2834512 197E-01 RCAN1

21 36715761 rs9979383 914E-02 RUNX1

21 43836186 rs11203203 106E-01 UBASH3A

22 21982892 rs2298428 964E-01 YDJC

22 37544810 rs3218253 100E-08 IL2RB





1-SNP model

Haplotypic risk

SNP alleles

(Mm)


(Mm)



AG 072 126

GG 023 143

GA 00002 -


CG 006 117

AA 023 118

AG 001 139

2p16-p15


AG 058 12

GG 038 136

GA 0005 -


AT 024 115

CA 006 120

AA 0 -


AG 021 118

GA 002 137

AA 002 155


CC 009 085

GA 004 062

GC 0 -



Chr POS Gene region

Lead SNP Low MAF

SNP

MAF

UNAFF

MAF

AFF

P OR r2

to lead

Location REG POT7X

CONS 17WA

Y


2 61391558 REL rs17008218 005 004 439E-05 083 1 INTRONIC 000 008

2 61581489 REL rs17009924 005 004 947E-05 084 092 INTRONIC 000 000

















GWAS IMMUNOCHIP


P OR

rs13315591a PXK 3 009 46x10-8 129 rs35677470 008 17 X 10-07 119 028 103 027 058

rs10488631 IRF5 7 011 42x10-11 119 rs3807306 049 19 X 10-07 089 18 X 10-05 11 02 1

rs934734 SPRED2 2 049 53x10-10 113 rs6546146 038 80 X 10-07 09 30 X 10-04 107 053 095

rs3761847 TRAF1 9 043 21x10-7 113 rs10739580 033 17 X 10-06 112 17 X 10-04 107 074 1

rs2104286 IL2RA 10 027 2x10-3 092 rs10795791 04 30 X 10-06 109 10 X 10-04 091 025 1

rs11586238 CD2 1 024 1x10-5 113 rs798000 034 62 X 10-06 111 30 X 10-03 107 033 072

rs10919563 PTPRC 1 013 2x10-4 088 rs2014863 036 21 X 10-05 109 77 X 10-04 091 007 1

rs1678542 KIF5A 12 038 2x10-4 091 rs10683701 033 23 X 10-05 09 10 X 10-03 093 027 058

rs548234 PRDM1 6 033 97x10-5 11 rs6911690 012 12 X 10-04 087 002 104 01 1

rs6822844 IL2-IL21 4 018 7x10-4 09 rs78560100 007 58 X 10-04 113 001 094 002 1

rs540386b TRAF6 11 014 3x10-4 088 rs570676 038 21 X 10-03 093 007 095 018 1




Region size


Region size


LD SNPS (ns)

r2gt09




PTPN22 1p13 113863087-

114527968

665kb

rs2476601b 114303808-114377568



ANKRD55 5q11 55414956-

55447909

33kb

rs71624119a 55440730-55442249


TNFAIP3 6q23 137896596-

138125335

229kb

rs6920220b 137959235-138006504

4727kb 761 (0) 9 (0) 18185kb 5 of TNFAIP3

TNFAIP3 6q23 137896596-

138125335

229kb

rs58721818g 138178293-

138243739

6545kb 835 (38) 7 (0) TNFAIP3

RBPJ 4p15 26028805-

26134465

106kb

rs932036a 26085480-26128710

4323kb 486 (0) 25 (0) 3637kb 5 of RBPJ

CCR6 6q27 167355854-

167547954

192kb

rs59466457b 167526096-

167540842

1475kb 234 (0) 6 (0) Intron 1 of CCR6

STAT4 2q32 191873553-

192007734

134kb

rs13426947a 191900449-191935804


STAT4 2q32 191873553- 134kb rs932169e 191929278-191929278



192007734

CCL21 9p13 34649442-

34974974

325kb rs2812378b 34707373-34710338

297kb 41 (4) 3 (0) CCL21

CD40 20q13 44594228-

44784336

190kb

rs6032662b 44730245-44747947


MMEL1 1p36 2406888-

2785671

378kb

rs2843401b 2516781-2709164

19238kb

4571 (73)

85 (1)


AFF3 2q11 100544954-

101038647

493kb

rs10209110a 100640432-100730111


REL 2p16 60914729-

61864047

949kb

rs34695944b 61072664-61164331

9167kb 876 (18) 14 (0) Complete REL

REL 2p16 60914729-

61864047

949kb

rs78404002g 61466603-61776131

30953kb

3579 (24)

5 (0)


USP34 SNORA70B XPO1

31596kb 3 of REL CTLA4 2q33 204678417-

204816382

138kb

rs11571302b 204738919-204745003


GIN1 5q21 102098582-

102711659

613kb

rs39984a 102595778-102625335

2956kb

385 (7)

40 (0)


13992kb 5of GIN1

PXK 3p14 58154177-

58549297

395kb

rs35677470a 58181499-58183636


13497kb 5 of PXK

IRF5 7q32 128549568- 228kb rs3807306b 128580680-128580680



128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884


SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300


TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485


CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)


CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515



PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































7 rs75351767 37427351 ELMO1 G 294E-07 11604 385E-05 11473 595E-05 11917


6 rs72928038 90976768 BACH2 A 823E-07 11282 112E-04 11156 216E-03 11207 T1D CD

3 rs1875463 143165502 SLC9A9 A 151E-06 08996 288E-04 09119 475E-05 08709

10 rs12764378 63800004 ARID5B A 181E-05 10994 164E-06 11292 696E-01 10135


14 rs911263 68753593 ACTN1 G 459E-04 09302 228E-06 08924 833E-01 09934 T1D

10 rs3802604 8102272 GATA3 G 507E-05 10813 368E-06 11085 217E-01 10372


13 rs7993214 40350912 COG6 A 102E-04 09263 455E-06 09005 432E-01 09768


13 rs17230016 82338338 SPRY2 G 961E-06 08838 178E-04 0886 144E-03 08709






REL 2 61136129 rs13031237 140E-09 61136129 rs13031237 126E-11

SPRED2 2 65597671 rs11673987 349E-08 65598241 rs1858036 748E-10

AFF3 2 100806514 rs6712515 282E-11 100806514 rs6712515 200E-11

STAT4 2 191969879 rs10181656 234E-13 191921874 rs11893432 153E-11

CD28|CTLA4 2 204738919 rs3087243 748E-11 204738919 rs3087243 388E-11

RBPJ 4 26086569 rs17630466 567E-13 26104113 rs12506688 600E-13

ANKRD55 5 55440730 rs71624119 568E-20 55440730 rs71624119 120E-11

GIN1 5 102608924 rs2561477 652E-10 102608924 rs2561477 856E-08

TNFAIP3 6 138006504 rs6920220 424E-15 138006504 rs6920220 355E-18

TAGAP 6 159489791 rs212389 299E-05 159489791 rs212389 911E-09

CCR6 6 167540842 rs1571878 229E-08 167540842 rs1571878 123E-12

IRF5 7 128580680 rs3807306 712E-10 128580680 rs3807306 475E-10

CCL21 9 34710260 rs2812378 850E-09 34710260 rs2812378 126E-09

TRAF1 9 123683569 rs2269060 371E-07 123683569 rs2269060 173E-08

IL2RA 10 6108340 rs10795791 111E-09 6108340 rs10795791 119E-09

DDX6 11 118611781 rs10892279 295E-08 118611781 rs10892279 134E-10


POU3F1 1 38616871 rs883220 119E-07 38616871 rs883220 209E-08

IL6R 1 154426970 rs2228145 130E-08 154426970 rs2228145 158E-07

GATA3 10 8095340 rs2275806 738E-08 8095340 rs2275806 458E-08

ARID5B 10 63800004 rs12764378 100E-08 63800004 rs12764378 445E-10

CD5 11 60909581 rs595158 335E-08 60909581 rs595158 556E-06

RASGRP1 15 38828140 rs8043085 176E-08 38828140 rs8043085 482E-11

TLE3 15 69991417 rs8026898 603E-11 69991417 rs8026898 652E-12

IRF8 16 86019087 rs13330176 168E-07 86019087 rs13330176 530E-09

IKZF3 17 38062196 rs2305480 420E-09 38040763 rs2872507 279E-09

TYK2 19 10463118 rs34536443 269E-13 10463118 rs34536443 224E-14

RCAN1 21 35911599 rs2834512 431E-07 35911599 rs2834512 306E-08

RUNX1 21 36715761 rs9979383 503E-10 36715761 rs9979383 369E-08





(OR) META ACPA-



META OR of OR ( OR)


1 rs2476601 114179091 PTPN22 923E-78 179 260E-04 118 244E-19 149

6 rs59466457 167457744 CCR6 477E-10 114 684E-01 099 100E-06 116

20 rs6032662 44167717 CD40 422E-09 086 831E-01 101 596E-06 085

15 rs8043085 36615432 RASGRP1 345E-10 117 363E-01 103 213E-04 114

6 rs629326 159416701 TAGAP 259E-06 090 717E-01 101 236E-04 089

11 rs4938573 118247052 DDX6 484E-07 087 596E-01 098 146E-03 089

15 rs77397211 36757788 RASGRP1 110E-03 115 524E-01 096 153E-03 121

2 rs34695944 60978354 REL 176E-08 113 359E-01 103 181E-03 110

1 rs2843401 2517993 MMEL1 800E-09 087 541E-01 098 188E-03 090

6 rs58721818 138285432 TNFAIP3 594E-12 146 899E-02 114 215E-03 127

2 rs6546146 65409828 SPRED2 603E-07 089 508E-01 098 220E-03 091

19 rs34536443 10324118 TYK2 303E-14 062 750E-03 082 295E-03 077

16 rs13330176 84576588 IRF8 872E-08 114 726E-01 101 340E-03 111

10 rs12722508 6128749 IL2RA 201E-05 085 891E-01 101 367E-03 086

1 rs798000 117082219 CD2 431E-06 111 469E-01 102 727E-03 109

10 rs12764378 63470010 ARID5B 900E-07 113 656E-01 102 881E-03 110

2 rs11571302 204451179 CTLA4CD28 456E-08 089 105E-01 096 890E-03 092

6 rs6920220 138048197 TNFAIP3 309E-13 120 220E-02 108 986E-03 110

4 rs932036 25699960 RBPJ 355E-10 116 176E-02 108 178E-02 108

17 rs2872507 35294289 GSDML 131E-06 111 239E-01 103 276E-02 107

9 rs2812378 34700260 CCL21 518E-10 115 117E-02 108 356E-02 107

21 rs2834512 34833469 RCAN1 293E-04 088 507E-01 097 441E-02 091

17 rs12936409 35297175 GSDML 771E-07 111 113E-01 105 452E-02 106


5 rs71624119 55476487 ANKRD55 171E-11 084 623E-12 079 825E-02 107


8 rs4840565 11382954 BLK 343E-04 109 853E-05 113 332E-01 097

21 rs9979383 35637631 RUNX1 315E-05 091 990E-05 089 554E-01 102

5 rs39984 102625191 GIN1 383E-06 088 165E-04 087 761E-01 101

1 rs2014863 197076224 PTPRC 874E-04 108 835E-04 110 369E-01 097

2 rs932169 191637523 STAT4 239E-02 109 116E-03 118 120E-01 092

19 rs3176767 10310751 ICAM3 271E-05 111 191E-03 111 859E-01 101

4 rs78560100 123260921 IL2_21 117E-03 114 214E-03 118 641E-01 097

2 rs13426947 191641499 STAT4 494E-09 117 262E-03 111 170E-01 105

11 rs595158 60666157 CD5 176E-05 110 597E-03 108 642E-01 101

3 rs35677470 58158676 DNASE1L3 150E-06 121 928E-03 115 516E-01 104





1 2528133 rs2843401 709E-06 TNFRSF14

1 17674537 rs2240335 404E-02 PADI4

1 38616871 rs883220 967E-01 POU3F1

1 114377568 rs2476601 287E-05 PTPN22

1 117263138 rs11586238 369E-10 CD2

1 154426970 rs2228145 305E-05 IL6R

1 161467042 rs12746613 433E-06 FCGR2B

1 167411384 rs864537 220E-11 CD247

1 198700442 rs10919563 125E-10 PTPRC

2 61136129 rs13031237 218E-06 REL

2 65595586 rs934734 144E-01 SPRED2

2 100806940 rs11676922 537E-01 AFF3

2 191935804 rs10168266 961E-09 STAT4

2 204610396 rs1980422 277E-12 CD28

2 204738919 rs3087243 142E-11 ICOS

3 58556841 rs13315591 895E-01 DNASE1L3

4 26104113 rs12506688 739E-01 RBPJ

4 123509421 rs6822844 432E-09 IL2

5 55438580 rs6859219 100E+00 ANKRD55

5 102608924 rs2561477 936E-01 GIN1

6 106568034 rs548234 180E-04 PRDM1

6 138002637 rs10499194 212E-04 TNFAIP3

6 159482521 rs394581 162E-05 TAGAP

6 167540842 rs1571878 426E-07 CCR6

7 128594183 rs10488631 326E-04 IRF5

8 11343973 rs2736340 259E-02 BLK

9 34743681 rs951005 960E-06 CCL21

9 123640500 rs1953126 208E-06 TRAF1

10 6099045 rs2104286 441E-10 IL2RA

10 6393260 rs4750316 422E-08 PRKCQ

10 8095340 rs2275806 726E-05 GATA3

10 63800004 rs12764378 884E-01 ARID5B

11 36525293 rs540386 671E-11 RAG1

11 60909581 rs595158 399E-11 CD5

11 118611781 rs10892279 919E-01 DDX6

12 57968715 rs1678542 658E-01 B4GALNT1

15 38828140 rs8043085 682E-08 RASGRP1

15 69991417 rs8026898 943E-01 KIF23

16 86019087 rs13330176 300E-07 IRF8

17 38040763 rs2872507 247E-05 IKZF3

19 10295433 rs4804493 751E-01 DNMT1


20 44734310 rs6032662 438E-10 CD40

21 35911599 rs2834512 197E-01 RCAN1

21 36715761 rs9979383 914E-02 RUNX1

21 43836186 rs11203203 106E-01 UBASH3A

22 21982892 rs2298428 964E-01 YDJC

22 37544810 rs3218253 100E-08 IL2RB





1-SNP model

Haplotypic risk

SNP alleles

(Mm)


(Mm)



AG 072 126

GG 023 143

GA 00002 -


CG 006 117

AA 023 118

AG 001 139

2p16-p15


AG 058 12

GG 038 136

GA 0005 -


AT 024 115

CA 006 120

AA 0 -


AG 021 118

GA 002 137

AA 002 155


CC 009 085

GA 004 062

GC 0 -



Chr POS Gene region

Lead SNP Low MAF

SNP

MAF

UNAFF

MAF

AFF

P OR r2

to lead

Location REG POT7X

CONS 17WA

Y


2 61391558 REL rs17008218 005 004 439E-05 083 1 INTRONIC 000 008

2 61581489 REL rs17009924 005 004 947E-05 084 092 INTRONIC 000 000

















GWAS IMMUNOCHIP


P OR

rs13315591a PXK 3 009 46x10-8 129 rs35677470 008 17 X 10-07 119 028 103 027 058

rs10488631 IRF5 7 011 42x10-11 119 rs3807306 049 19 X 10-07 089 18 X 10-05 11 02 1

rs934734 SPRED2 2 049 53x10-10 113 rs6546146 038 80 X 10-07 09 30 X 10-04 107 053 095

rs3761847 TRAF1 9 043 21x10-7 113 rs10739580 033 17 X 10-06 112 17 X 10-04 107 074 1

rs2104286 IL2RA 10 027 2x10-3 092 rs10795791 04 30 X 10-06 109 10 X 10-04 091 025 1

rs11586238 CD2 1 024 1x10-5 113 rs798000 034 62 X 10-06 111 30 X 10-03 107 033 072

rs10919563 PTPRC 1 013 2x10-4 088 rs2014863 036 21 X 10-05 109 77 X 10-04 091 007 1

rs1678542 KIF5A 12 038 2x10-4 091 rs10683701 033 23 X 10-05 09 10 X 10-03 093 027 058

rs548234 PRDM1 6 033 97x10-5 11 rs6911690 012 12 X 10-04 087 002 104 01 1

rs6822844 IL2-IL21 4 018 7x10-4 09 rs78560100 007 58 X 10-04 113 001 094 002 1

rs540386b TRAF6 11 014 3x10-4 088 rs570676 038 21 X 10-03 093 007 095 018 1




Region size


Region size


LD SNPS (ns)

r2gt09




PTPN22 1p13 113863087-

114527968

665kb

rs2476601b 114303808-114377568



ANKRD55 5q11 55414956-

55447909

33kb

rs71624119a 55440730-55442249


TNFAIP3 6q23 137896596-

138125335

229kb

rs6920220b 137959235-138006504

4727kb 761 (0) 9 (0) 18185kb 5 of TNFAIP3

TNFAIP3 6q23 137896596-

138125335

229kb

rs58721818g 138178293-

138243739

6545kb 835 (38) 7 (0) TNFAIP3

RBPJ 4p15 26028805-

26134465

106kb

rs932036a 26085480-26128710

4323kb 486 (0) 25 (0) 3637kb 5 of RBPJ

CCR6 6q27 167355854-

167547954

192kb

rs59466457b 167526096-

167540842

1475kb 234 (0) 6 (0) Intron 1 of CCR6

STAT4 2q32 191873553-

192007734

134kb

rs13426947a 191900449-191935804


STAT4 2q32 191873553- 134kb rs932169e 191929278-191929278



192007734

CCL21 9p13 34649442-

34974974

325kb rs2812378b 34707373-34710338

297kb 41 (4) 3 (0) CCL21

CD40 20q13 44594228-

44784336

190kb

rs6032662b 44730245-44747947


MMEL1 1p36 2406888-

2785671

378kb

rs2843401b 2516781-2709164

19238kb

4571 (73)

85 (1)


AFF3 2q11 100544954-

101038647

493kb

rs10209110a 100640432-100730111


REL 2p16 60914729-

61864047

949kb

rs34695944b 61072664-61164331

9167kb 876 (18) 14 (0) Complete REL

REL 2p16 60914729-

61864047

949kb

rs78404002g 61466603-61776131

30953kb

3579 (24)

5 (0)


USP34 SNORA70B XPO1

31596kb 3 of REL CTLA4 2q33 204678417-

204816382

138kb

rs11571302b 204738919-204745003


GIN1 5q21 102098582-

102711659

613kb

rs39984a 102595778-102625335

2956kb

385 (7)

40 (0)


13992kb 5of GIN1

PXK 3p14 58154177-

58549297

395kb

rs35677470a 58181499-58183636


13497kb 5 of PXK

IRF5 7q32 128549568- 228kb rs3807306b 128580680-128580680



128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884


SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300


TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485


CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)


CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515



PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40



















































REL 2 61136129 rs13031237 140E-09 61136129 rs13031237 126E-11

SPRED2 2 65597671 rs11673987 349E-08 65598241 rs1858036 748E-10

AFF3 2 100806514 rs6712515 282E-11 100806514 rs6712515 200E-11

STAT4 2 191969879 rs10181656 234E-13 191921874 rs11893432 153E-11

CD28|CTLA4 2 204738919 rs3087243 748E-11 204738919 rs3087243 388E-11

RBPJ 4 26086569 rs17630466 567E-13 26104113 rs12506688 600E-13

ANKRD55 5 55440730 rs71624119 568E-20 55440730 rs71624119 120E-11

GIN1 5 102608924 rs2561477 652E-10 102608924 rs2561477 856E-08

TNFAIP3 6 138006504 rs6920220 424E-15 138006504 rs6920220 355E-18

TAGAP 6 159489791 rs212389 299E-05 159489791 rs212389 911E-09

CCR6 6 167540842 rs1571878 229E-08 167540842 rs1571878 123E-12

IRF5 7 128580680 rs3807306 712E-10 128580680 rs3807306 475E-10

CCL21 9 34710260 rs2812378 850E-09 34710260 rs2812378 126E-09

TRAF1 9 123683569 rs2269060 371E-07 123683569 rs2269060 173E-08

IL2RA 10 6108340 rs10795791 111E-09 6108340 rs10795791 119E-09

DDX6 11 118611781 rs10892279 295E-08 118611781 rs10892279 134E-10


POU3F1 1 38616871 rs883220 119E-07 38616871 rs883220 209E-08

IL6R 1 154426970 rs2228145 130E-08 154426970 rs2228145 158E-07

GATA3 10 8095340 rs2275806 738E-08 8095340 rs2275806 458E-08

ARID5B 10 63800004 rs12764378 100E-08 63800004 rs12764378 445E-10

CD5 11 60909581 rs595158 335E-08 60909581 rs595158 556E-06

RASGRP1 15 38828140 rs8043085 176E-08 38828140 rs8043085 482E-11

TLE3 15 69991417 rs8026898 603E-11 69991417 rs8026898 652E-12

IRF8 16 86019087 rs13330176 168E-07 86019087 rs13330176 530E-09

IKZF3 17 38062196 rs2305480 420E-09 38040763 rs2872507 279E-09

TYK2 19 10463118 rs34536443 269E-13 10463118 rs34536443 224E-14

RCAN1 21 35911599 rs2834512 431E-07 35911599 rs2834512 306E-08

RUNX1 21 36715761 rs9979383 503E-10 36715761 rs9979383 369E-08





(OR) META ACPA-



META OR of OR ( OR)


1 rs2476601 114179091 PTPN22 923E-78 179 260E-04 118 244E-19 149

6 rs59466457 167457744 CCR6 477E-10 114 684E-01 099 100E-06 116

20 rs6032662 44167717 CD40 422E-09 086 831E-01 101 596E-06 085

15 rs8043085 36615432 RASGRP1 345E-10 117 363E-01 103 213E-04 114

6 rs629326 159416701 TAGAP 259E-06 090 717E-01 101 236E-04 089

11 rs4938573 118247052 DDX6 484E-07 087 596E-01 098 146E-03 089

15 rs77397211 36757788 RASGRP1 110E-03 115 524E-01 096 153E-03 121

2 rs34695944 60978354 REL 176E-08 113 359E-01 103 181E-03 110

1 rs2843401 2517993 MMEL1 800E-09 087 541E-01 098 188E-03 090

6 rs58721818 138285432 TNFAIP3 594E-12 146 899E-02 114 215E-03 127

2 rs6546146 65409828 SPRED2 603E-07 089 508E-01 098 220E-03 091

19 rs34536443 10324118 TYK2 303E-14 062 750E-03 082 295E-03 077

16 rs13330176 84576588 IRF8 872E-08 114 726E-01 101 340E-03 111

10 rs12722508 6128749 IL2RA 201E-05 085 891E-01 101 367E-03 086

1 rs798000 117082219 CD2 431E-06 111 469E-01 102 727E-03 109

10 rs12764378 63470010 ARID5B 900E-07 113 656E-01 102 881E-03 110

2 rs11571302 204451179 CTLA4CD28 456E-08 089 105E-01 096 890E-03 092

6 rs6920220 138048197 TNFAIP3 309E-13 120 220E-02 108 986E-03 110

4 rs932036 25699960 RBPJ 355E-10 116 176E-02 108 178E-02 108

17 rs2872507 35294289 GSDML 131E-06 111 239E-01 103 276E-02 107

9 rs2812378 34700260 CCL21 518E-10 115 117E-02 108 356E-02 107

21 rs2834512 34833469 RCAN1 293E-04 088 507E-01 097 441E-02 091

17 rs12936409 35297175 GSDML 771E-07 111 113E-01 105 452E-02 106


5 rs71624119 55476487 ANKRD55 171E-11 084 623E-12 079 825E-02 107


8 rs4840565 11382954 BLK 343E-04 109 853E-05 113 332E-01 097

21 rs9979383 35637631 RUNX1 315E-05 091 990E-05 089 554E-01 102

5 rs39984 102625191 GIN1 383E-06 088 165E-04 087 761E-01 101

1 rs2014863 197076224 PTPRC 874E-04 108 835E-04 110 369E-01 097

2 rs932169 191637523 STAT4 239E-02 109 116E-03 118 120E-01 092

19 rs3176767 10310751 ICAM3 271E-05 111 191E-03 111 859E-01 101

4 rs78560100 123260921 IL2_21 117E-03 114 214E-03 118 641E-01 097

2 rs13426947 191641499 STAT4 494E-09 117 262E-03 111 170E-01 105

11 rs595158 60666157 CD5 176E-05 110 597E-03 108 642E-01 101

3 rs35677470 58158676 DNASE1L3 150E-06 121 928E-03 115 516E-01 104





1 2528133 rs2843401 709E-06 TNFRSF14

1 17674537 rs2240335 404E-02 PADI4

1 38616871 rs883220 967E-01 POU3F1

1 114377568 rs2476601 287E-05 PTPN22

1 117263138 rs11586238 369E-10 CD2

1 154426970 rs2228145 305E-05 IL6R

1 161467042 rs12746613 433E-06 FCGR2B

1 167411384 rs864537 220E-11 CD247

1 198700442 rs10919563 125E-10 PTPRC

2 61136129 rs13031237 218E-06 REL

2 65595586 rs934734 144E-01 SPRED2

2 100806940 rs11676922 537E-01 AFF3

2 191935804 rs10168266 961E-09 STAT4

2 204610396 rs1980422 277E-12 CD28

2 204738919 rs3087243 142E-11 ICOS

3 58556841 rs13315591 895E-01 DNASE1L3

4 26104113 rs12506688 739E-01 RBPJ

4 123509421 rs6822844 432E-09 IL2

5 55438580 rs6859219 100E+00 ANKRD55

5 102608924 rs2561477 936E-01 GIN1

6 106568034 rs548234 180E-04 PRDM1

6 138002637 rs10499194 212E-04 TNFAIP3

6 159482521 rs394581 162E-05 TAGAP

6 167540842 rs1571878 426E-07 CCR6

7 128594183 rs10488631 326E-04 IRF5

8 11343973 rs2736340 259E-02 BLK

9 34743681 rs951005 960E-06 CCL21

9 123640500 rs1953126 208E-06 TRAF1

10 6099045 rs2104286 441E-10 IL2RA

10 6393260 rs4750316 422E-08 PRKCQ

10 8095340 rs2275806 726E-05 GATA3

10 63800004 rs12764378 884E-01 ARID5B

11 36525293 rs540386 671E-11 RAG1

11 60909581 rs595158 399E-11 CD5

11 118611781 rs10892279 919E-01 DDX6

12 57968715 rs1678542 658E-01 B4GALNT1

15 38828140 rs8043085 682E-08 RASGRP1

15 69991417 rs8026898 943E-01 KIF23

16 86019087 rs13330176 300E-07 IRF8

17 38040763 rs2872507 247E-05 IKZF3

19 10295433 rs4804493 751E-01 DNMT1


20 44734310 rs6032662 438E-10 CD40

21 35911599 rs2834512 197E-01 RCAN1

21 36715761 rs9979383 914E-02 RUNX1

21 43836186 rs11203203 106E-01 UBASH3A

22 21982892 rs2298428 964E-01 YDJC

22 37544810 rs3218253 100E-08 IL2RB





1-SNP model

Haplotypic risk

SNP alleles

(Mm)


(Mm)



AG 072 126

GG 023 143

GA 00002 -


CG 006 117

AA 023 118

AG 001 139

2p16-p15


AG 058 12

GG 038 136

GA 0005 -


AT 024 115

CA 006 120

AA 0 -


AG 021 118

GA 002 137

AA 002 155


CC 009 085

GA 004 062

GC 0 -



Chr POS Gene region

Lead SNP Low MAF

SNP

MAF

UNAFF

MAF

AFF

P OR r2

to lead

Location REG POT7X

CONS 17WA

Y


2 61391558 REL rs17008218 005 004 439E-05 083 1 INTRONIC 000 008

2 61581489 REL rs17009924 005 004 947E-05 084 092 INTRONIC 000 000

















GWAS IMMUNOCHIP


P OR

rs13315591a PXK 3 009 46x10-8 129 rs35677470 008 17 X 10-07 119 028 103 027 058

rs10488631 IRF5 7 011 42x10-11 119 rs3807306 049 19 X 10-07 089 18 X 10-05 11 02 1

rs934734 SPRED2 2 049 53x10-10 113 rs6546146 038 80 X 10-07 09 30 X 10-04 107 053 095

rs3761847 TRAF1 9 043 21x10-7 113 rs10739580 033 17 X 10-06 112 17 X 10-04 107 074 1

rs2104286 IL2RA 10 027 2x10-3 092 rs10795791 04 30 X 10-06 109 10 X 10-04 091 025 1

rs11586238 CD2 1 024 1x10-5 113 rs798000 034 62 X 10-06 111 30 X 10-03 107 033 072

rs10919563 PTPRC 1 013 2x10-4 088 rs2014863 036 21 X 10-05 109 77 X 10-04 091 007 1

rs1678542 KIF5A 12 038 2x10-4 091 rs10683701 033 23 X 10-05 09 10 X 10-03 093 027 058

rs548234 PRDM1 6 033 97x10-5 11 rs6911690 012 12 X 10-04 087 002 104 01 1

rs6822844 IL2-IL21 4 018 7x10-4 09 rs78560100 007 58 X 10-04 113 001 094 002 1

rs540386b TRAF6 11 014 3x10-4 088 rs570676 038 21 X 10-03 093 007 095 018 1




Region size


Region size


LD SNPS (ns)

r2gt09




PTPN22 1p13 113863087-

114527968

665kb

rs2476601b 114303808-114377568



ANKRD55 5q11 55414956-

55447909

33kb

rs71624119a 55440730-55442249


TNFAIP3 6q23 137896596-

138125335

229kb

rs6920220b 137959235-138006504

4727kb 761 (0) 9 (0) 18185kb 5 of TNFAIP3

TNFAIP3 6q23 137896596-

138125335

229kb

rs58721818g 138178293-

138243739

6545kb 835 (38) 7 (0) TNFAIP3

RBPJ 4p15 26028805-

26134465

106kb

rs932036a 26085480-26128710

4323kb 486 (0) 25 (0) 3637kb 5 of RBPJ

CCR6 6q27 167355854-

167547954

192kb

rs59466457b 167526096-

167540842

1475kb 234 (0) 6 (0) Intron 1 of CCR6

STAT4 2q32 191873553-

192007734

134kb

rs13426947a 191900449-191935804


STAT4 2q32 191873553- 134kb rs932169e 191929278-191929278



192007734

CCL21 9p13 34649442-

34974974

325kb rs2812378b 34707373-34710338

297kb 41 (4) 3 (0) CCL21

CD40 20q13 44594228-

44784336

190kb

rs6032662b 44730245-44747947


MMEL1 1p36 2406888-

2785671

378kb

rs2843401b 2516781-2709164

19238kb

4571 (73)

85 (1)


AFF3 2q11 100544954-

101038647

493kb

rs10209110a 100640432-100730111


REL 2p16 60914729-

61864047

949kb

rs34695944b 61072664-61164331

9167kb 876 (18) 14 (0) Complete REL

REL 2p16 60914729-

61864047

949kb

rs78404002g 61466603-61776131

30953kb

3579 (24)

5 (0)


USP34 SNORA70B XPO1

31596kb 3 of REL CTLA4 2q33 204678417-

204816382

138kb

rs11571302b 204738919-204745003


GIN1 5q21 102098582-

102711659

613kb

rs39984a 102595778-102625335

2956kb

385 (7)

40 (0)


13992kb 5of GIN1

PXK 3p14 58154177-

58549297

395kb

rs35677470a 58181499-58183636


13497kb 5 of PXK

IRF5 7q32 128549568- 228kb rs3807306b 128580680-128580680



128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884


SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300


TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485


CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)


CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515



PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40




















































(OR) META ACPA-



META OR of OR ( OR)


1 rs2476601 114179091 PTPN22 923E-78 179 260E-04 118 244E-19 149

6 rs59466457 167457744 CCR6 477E-10 114 684E-01 099 100E-06 116

20 rs6032662 44167717 CD40 422E-09 086 831E-01 101 596E-06 085

15 rs8043085 36615432 RASGRP1 345E-10 117 363E-01 103 213E-04 114

6 rs629326 159416701 TAGAP 259E-06 090 717E-01 101 236E-04 089

11 rs4938573 118247052 DDX6 484E-07 087 596E-01 098 146E-03 089

15 rs77397211 36757788 RASGRP1 110E-03 115 524E-01 096 153E-03 121

2 rs34695944 60978354 REL 176E-08 113 359E-01 103 181E-03 110

1 rs2843401 2517993 MMEL1 800E-09 087 541E-01 098 188E-03 090

6 rs58721818 138285432 TNFAIP3 594E-12 146 899E-02 114 215E-03 127

2 rs6546146 65409828 SPRED2 603E-07 089 508E-01 098 220E-03 091

19 rs34536443 10324118 TYK2 303E-14 062 750E-03 082 295E-03 077

16 rs13330176 84576588 IRF8 872E-08 114 726E-01 101 340E-03 111

10 rs12722508 6128749 IL2RA 201E-05 085 891E-01 101 367E-03 086

1 rs798000 117082219 CD2 431E-06 111 469E-01 102 727E-03 109

10 rs12764378 63470010 ARID5B 900E-07 113 656E-01 102 881E-03 110

2 rs11571302 204451179 CTLA4CD28 456E-08 089 105E-01 096 890E-03 092

6 rs6920220 138048197 TNFAIP3 309E-13 120 220E-02 108 986E-03 110

4 rs932036 25699960 RBPJ 355E-10 116 176E-02 108 178E-02 108

17 rs2872507 35294289 GSDML 131E-06 111 239E-01 103 276E-02 107

9 rs2812378 34700260 CCL21 518E-10 115 117E-02 108 356E-02 107

21 rs2834512 34833469 RCAN1 293E-04 088 507E-01 097 441E-02 091

17 rs12936409 35297175 GSDML 771E-07 111 113E-01 105 452E-02 106


5 rs71624119 55476487 ANKRD55 171E-11 084 623E-12 079 825E-02 107


8 rs4840565 11382954 BLK 343E-04 109 853E-05 113 332E-01 097

21 rs9979383 35637631 RUNX1 315E-05 091 990E-05 089 554E-01 102

5 rs39984 102625191 GIN1 383E-06 088 165E-04 087 761E-01 101

1 rs2014863 197076224 PTPRC 874E-04 108 835E-04 110 369E-01 097

2 rs932169 191637523 STAT4 239E-02 109 116E-03 118 120E-01 092

19 rs3176767 10310751 ICAM3 271E-05 111 191E-03 111 859E-01 101

4 rs78560100 123260921 IL2_21 117E-03 114 214E-03 118 641E-01 097

2 rs13426947 191641499 STAT4 494E-09 117 262E-03 111 170E-01 105

11 rs595158 60666157 CD5 176E-05 110 597E-03 108 642E-01 101

3 rs35677470 58158676 DNASE1L3 150E-06 121 928E-03 115 516E-01 104





1 2528133 rs2843401 709E-06 TNFRSF14

1 17674537 rs2240335 404E-02 PADI4

1 38616871 rs883220 967E-01 POU3F1

1 114377568 rs2476601 287E-05 PTPN22

1 117263138 rs11586238 369E-10 CD2

1 154426970 rs2228145 305E-05 IL6R

1 161467042 rs12746613 433E-06 FCGR2B

1 167411384 rs864537 220E-11 CD247

1 198700442 rs10919563 125E-10 PTPRC

2 61136129 rs13031237 218E-06 REL

2 65595586 rs934734 144E-01 SPRED2

2 100806940 rs11676922 537E-01 AFF3

2 191935804 rs10168266 961E-09 STAT4

2 204610396 rs1980422 277E-12 CD28

2 204738919 rs3087243 142E-11 ICOS

3 58556841 rs13315591 895E-01 DNASE1L3

4 26104113 rs12506688 739E-01 RBPJ

4 123509421 rs6822844 432E-09 IL2

5 55438580 rs6859219 100E+00 ANKRD55

5 102608924 rs2561477 936E-01 GIN1

6 106568034 rs548234 180E-04 PRDM1

6 138002637 rs10499194 212E-04 TNFAIP3

6 159482521 rs394581 162E-05 TAGAP

6 167540842 rs1571878 426E-07 CCR6

7 128594183 rs10488631 326E-04 IRF5

8 11343973 rs2736340 259E-02 BLK

9 34743681 rs951005 960E-06 CCL21

9 123640500 rs1953126 208E-06 TRAF1

10 6099045 rs2104286 441E-10 IL2RA

10 6393260 rs4750316 422E-08 PRKCQ

10 8095340 rs2275806 726E-05 GATA3

10 63800004 rs12764378 884E-01 ARID5B

11 36525293 rs540386 671E-11 RAG1

11 60909581 rs595158 399E-11 CD5

11 118611781 rs10892279 919E-01 DDX6

12 57968715 rs1678542 658E-01 B4GALNT1

15 38828140 rs8043085 682E-08 RASGRP1

15 69991417 rs8026898 943E-01 KIF23

16 86019087 rs13330176 300E-07 IRF8

17 38040763 rs2872507 247E-05 IKZF3

19 10295433 rs4804493 751E-01 DNMT1


20 44734310 rs6032662 438E-10 CD40

21 35911599 rs2834512 197E-01 RCAN1

21 36715761 rs9979383 914E-02 RUNX1

21 43836186 rs11203203 106E-01 UBASH3A

22 21982892 rs2298428 964E-01 YDJC

22 37544810 rs3218253 100E-08 IL2RB





1-SNP model

Haplotypic risk

SNP alleles

(Mm)


(Mm)



AG 072 126

GG 023 143

GA 00002 -


CG 006 117

AA 023 118

AG 001 139

2p16-p15


AG 058 12

GG 038 136

GA 0005 -


AT 024 115

CA 006 120

AA 0 -


AG 021 118

GA 002 137

AA 002 155


CC 009 085

GA 004 062

GC 0 -



Chr POS Gene region

Lead SNP Low MAF

SNP

MAF

UNAFF

MAF

AFF

P OR r2

to lead

Location REG POT7X

CONS 17WA

Y


2 61391558 REL rs17008218 005 004 439E-05 083 1 INTRONIC 000 008

2 61581489 REL rs17009924 005 004 947E-05 084 092 INTRONIC 000 000

















GWAS IMMUNOCHIP


P OR

rs13315591a PXK 3 009 46x10-8 129 rs35677470 008 17 X 10-07 119 028 103 027 058

rs10488631 IRF5 7 011 42x10-11 119 rs3807306 049 19 X 10-07 089 18 X 10-05 11 02 1

rs934734 SPRED2 2 049 53x10-10 113 rs6546146 038 80 X 10-07 09 30 X 10-04 107 053 095

rs3761847 TRAF1 9 043 21x10-7 113 rs10739580 033 17 X 10-06 112 17 X 10-04 107 074 1

rs2104286 IL2RA 10 027 2x10-3 092 rs10795791 04 30 X 10-06 109 10 X 10-04 091 025 1

rs11586238 CD2 1 024 1x10-5 113 rs798000 034 62 X 10-06 111 30 X 10-03 107 033 072

rs10919563 PTPRC 1 013 2x10-4 088 rs2014863 036 21 X 10-05 109 77 X 10-04 091 007 1

rs1678542 KIF5A 12 038 2x10-4 091 rs10683701 033 23 X 10-05 09 10 X 10-03 093 027 058

rs548234 PRDM1 6 033 97x10-5 11 rs6911690 012 12 X 10-04 087 002 104 01 1

rs6822844 IL2-IL21 4 018 7x10-4 09 rs78560100 007 58 X 10-04 113 001 094 002 1

rs540386b TRAF6 11 014 3x10-4 088 rs570676 038 21 X 10-03 093 007 095 018 1




Region size


Region size


LD SNPS (ns)

r2gt09




PTPN22 1p13 113863087-

114527968

665kb

rs2476601b 114303808-114377568



ANKRD55 5q11 55414956-

55447909

33kb

rs71624119a 55440730-55442249


TNFAIP3 6q23 137896596-

138125335

229kb

rs6920220b 137959235-138006504

4727kb 761 (0) 9 (0) 18185kb 5 of TNFAIP3

TNFAIP3 6q23 137896596-

138125335

229kb

rs58721818g 138178293-

138243739

6545kb 835 (38) 7 (0) TNFAIP3

RBPJ 4p15 26028805-

26134465

106kb

rs932036a 26085480-26128710

4323kb 486 (0) 25 (0) 3637kb 5 of RBPJ

CCR6 6q27 167355854-

167547954

192kb

rs59466457b 167526096-

167540842

1475kb 234 (0) 6 (0) Intron 1 of CCR6

STAT4 2q32 191873553-

192007734

134kb

rs13426947a 191900449-191935804


STAT4 2q32 191873553- 134kb rs932169e 191929278-191929278



192007734

CCL21 9p13 34649442-

34974974

325kb rs2812378b 34707373-34710338

297kb 41 (4) 3 (0) CCL21

CD40 20q13 44594228-

44784336

190kb

rs6032662b 44730245-44747947


MMEL1 1p36 2406888-

2785671

378kb

rs2843401b 2516781-2709164

19238kb

4571 (73)

85 (1)


AFF3 2q11 100544954-

101038647

493kb

rs10209110a 100640432-100730111


REL 2p16 60914729-

61864047

949kb

rs34695944b 61072664-61164331

9167kb 876 (18) 14 (0) Complete REL

REL 2p16 60914729-

61864047

949kb

rs78404002g 61466603-61776131

30953kb

3579 (24)

5 (0)


USP34 SNORA70B XPO1

31596kb 3 of REL CTLA4 2q33 204678417-

204816382

138kb

rs11571302b 204738919-204745003


GIN1 5q21 102098582-

102711659

613kb

rs39984a 102595778-102625335

2956kb

385 (7)

40 (0)


13992kb 5of GIN1

PXK 3p14 58154177-

58549297

395kb

rs35677470a 58181499-58183636


13497kb 5 of PXK

IRF5 7q32 128549568- 228kb rs3807306b 128580680-128580680



128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884


SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300


TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485


CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)


CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515



PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































8 rs4840565 11382954 BLK 343E-04 109 853E-05 113 332E-01 097

21 rs9979383 35637631 RUNX1 315E-05 091 990E-05 089 554E-01 102

5 rs39984 102625191 GIN1 383E-06 088 165E-04 087 761E-01 101

1 rs2014863 197076224 PTPRC 874E-04 108 835E-04 110 369E-01 097

2 rs932169 191637523 STAT4 239E-02 109 116E-03 118 120E-01 092

19 rs3176767 10310751 ICAM3 271E-05 111 191E-03 111 859E-01 101

4 rs78560100 123260921 IL2_21 117E-03 114 214E-03 118 641E-01 097

2 rs13426947 191641499 STAT4 494E-09 117 262E-03 111 170E-01 105

11 rs595158 60666157 CD5 176E-05 110 597E-03 108 642E-01 101

3 rs35677470 58158676 DNASE1L3 150E-06 121 928E-03 115 516E-01 104





1 2528133 rs2843401 709E-06 TNFRSF14

1 17674537 rs2240335 404E-02 PADI4

1 38616871 rs883220 967E-01 POU3F1

1 114377568 rs2476601 287E-05 PTPN22

1 117263138 rs11586238 369E-10 CD2

1 154426970 rs2228145 305E-05 IL6R

1 161467042 rs12746613 433E-06 FCGR2B

1 167411384 rs864537 220E-11 CD247

1 198700442 rs10919563 125E-10 PTPRC

2 61136129 rs13031237 218E-06 REL

2 65595586 rs934734 144E-01 SPRED2

2 100806940 rs11676922 537E-01 AFF3

2 191935804 rs10168266 961E-09 STAT4

2 204610396 rs1980422 277E-12 CD28

2 204738919 rs3087243 142E-11 ICOS

3 58556841 rs13315591 895E-01 DNASE1L3

4 26104113 rs12506688 739E-01 RBPJ

4 123509421 rs6822844 432E-09 IL2

5 55438580 rs6859219 100E+00 ANKRD55

5 102608924 rs2561477 936E-01 GIN1

6 106568034 rs548234 180E-04 PRDM1

6 138002637 rs10499194 212E-04 TNFAIP3

6 159482521 rs394581 162E-05 TAGAP

6 167540842 rs1571878 426E-07 CCR6

7 128594183 rs10488631 326E-04 IRF5

8 11343973 rs2736340 259E-02 BLK

9 34743681 rs951005 960E-06 CCL21

9 123640500 rs1953126 208E-06 TRAF1

10 6099045 rs2104286 441E-10 IL2RA

10 6393260 rs4750316 422E-08 PRKCQ

10 8095340 rs2275806 726E-05 GATA3

10 63800004 rs12764378 884E-01 ARID5B

11 36525293 rs540386 671E-11 RAG1

11 60909581 rs595158 399E-11 CD5

11 118611781 rs10892279 919E-01 DDX6

12 57968715 rs1678542 658E-01 B4GALNT1

15 38828140 rs8043085 682E-08 RASGRP1

15 69991417 rs8026898 943E-01 KIF23

16 86019087 rs13330176 300E-07 IRF8

17 38040763 rs2872507 247E-05 IKZF3

19 10295433 rs4804493 751E-01 DNMT1


20 44734310 rs6032662 438E-10 CD40

21 35911599 rs2834512 197E-01 RCAN1

21 36715761 rs9979383 914E-02 RUNX1

21 43836186 rs11203203 106E-01 UBASH3A

22 21982892 rs2298428 964E-01 YDJC

22 37544810 rs3218253 100E-08 IL2RB





1-SNP model

Haplotypic risk

SNP alleles

(Mm)


(Mm)



AG 072 126

GG 023 143

GA 00002 -


CG 006 117

AA 023 118

AG 001 139

2p16-p15


AG 058 12

GG 038 136

GA 0005 -


AT 024 115

CA 006 120

AA 0 -


AG 021 118

GA 002 137

AA 002 155


CC 009 085

GA 004 062

GC 0 -



Chr POS Gene region

Lead SNP Low MAF

SNP

MAF

UNAFF

MAF

AFF

P OR r2

to lead

Location REG POT7X

CONS 17WA

Y


2 61391558 REL rs17008218 005 004 439E-05 083 1 INTRONIC 000 008

2 61581489 REL rs17009924 005 004 947E-05 084 092 INTRONIC 000 000

















GWAS IMMUNOCHIP


P OR

rs13315591a PXK 3 009 46x10-8 129 rs35677470 008 17 X 10-07 119 028 103 027 058

rs10488631 IRF5 7 011 42x10-11 119 rs3807306 049 19 X 10-07 089 18 X 10-05 11 02 1

rs934734 SPRED2 2 049 53x10-10 113 rs6546146 038 80 X 10-07 09 30 X 10-04 107 053 095

rs3761847 TRAF1 9 043 21x10-7 113 rs10739580 033 17 X 10-06 112 17 X 10-04 107 074 1

rs2104286 IL2RA 10 027 2x10-3 092 rs10795791 04 30 X 10-06 109 10 X 10-04 091 025 1

rs11586238 CD2 1 024 1x10-5 113 rs798000 034 62 X 10-06 111 30 X 10-03 107 033 072

rs10919563 PTPRC 1 013 2x10-4 088 rs2014863 036 21 X 10-05 109 77 X 10-04 091 007 1

rs1678542 KIF5A 12 038 2x10-4 091 rs10683701 033 23 X 10-05 09 10 X 10-03 093 027 058

rs548234 PRDM1 6 033 97x10-5 11 rs6911690 012 12 X 10-04 087 002 104 01 1

rs6822844 IL2-IL21 4 018 7x10-4 09 rs78560100 007 58 X 10-04 113 001 094 002 1

rs540386b TRAF6 11 014 3x10-4 088 rs570676 038 21 X 10-03 093 007 095 018 1




Region size


Region size


LD SNPS (ns)

r2gt09




PTPN22 1p13 113863087-

114527968

665kb

rs2476601b 114303808-114377568



ANKRD55 5q11 55414956-

55447909

33kb

rs71624119a 55440730-55442249


TNFAIP3 6q23 137896596-

138125335

229kb

rs6920220b 137959235-138006504

4727kb 761 (0) 9 (0) 18185kb 5 of TNFAIP3

TNFAIP3 6q23 137896596-

138125335

229kb

rs58721818g 138178293-

138243739

6545kb 835 (38) 7 (0) TNFAIP3

RBPJ 4p15 26028805-

26134465

106kb

rs932036a 26085480-26128710

4323kb 486 (0) 25 (0) 3637kb 5 of RBPJ

CCR6 6q27 167355854-

167547954

192kb

rs59466457b 167526096-

167540842

1475kb 234 (0) 6 (0) Intron 1 of CCR6

STAT4 2q32 191873553-

192007734

134kb

rs13426947a 191900449-191935804


STAT4 2q32 191873553- 134kb rs932169e 191929278-191929278



192007734

CCL21 9p13 34649442-

34974974

325kb rs2812378b 34707373-34710338

297kb 41 (4) 3 (0) CCL21

CD40 20q13 44594228-

44784336

190kb

rs6032662b 44730245-44747947


MMEL1 1p36 2406888-

2785671

378kb

rs2843401b 2516781-2709164

19238kb

4571 (73)

85 (1)


AFF3 2q11 100544954-

101038647

493kb

rs10209110a 100640432-100730111


REL 2p16 60914729-

61864047

949kb

rs34695944b 61072664-61164331

9167kb 876 (18) 14 (0) Complete REL

REL 2p16 60914729-

61864047

949kb

rs78404002g 61466603-61776131

30953kb

3579 (24)

5 (0)


USP34 SNORA70B XPO1

31596kb 3 of REL CTLA4 2q33 204678417-

204816382

138kb

rs11571302b 204738919-204745003


GIN1 5q21 102098582-

102711659

613kb

rs39984a 102595778-102625335

2956kb

385 (7)

40 (0)


13992kb 5of GIN1

PXK 3p14 58154177-

58549297

395kb

rs35677470a 58181499-58183636


13497kb 5 of PXK

IRF5 7q32 128549568- 228kb rs3807306b 128580680-128580680



128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884


SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300


TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485


CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)


CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515



PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40




















































1 2528133 rs2843401 709E-06 TNFRSF14

1 17674537 rs2240335 404E-02 PADI4

1 38616871 rs883220 967E-01 POU3F1

1 114377568 rs2476601 287E-05 PTPN22

1 117263138 rs11586238 369E-10 CD2

1 154426970 rs2228145 305E-05 IL6R

1 161467042 rs12746613 433E-06 FCGR2B

1 167411384 rs864537 220E-11 CD247

1 198700442 rs10919563 125E-10 PTPRC

2 61136129 rs13031237 218E-06 REL

2 65595586 rs934734 144E-01 SPRED2

2 100806940 rs11676922 537E-01 AFF3

2 191935804 rs10168266 961E-09 STAT4

2 204610396 rs1980422 277E-12 CD28

2 204738919 rs3087243 142E-11 ICOS

3 58556841 rs13315591 895E-01 DNASE1L3

4 26104113 rs12506688 739E-01 RBPJ

4 123509421 rs6822844 432E-09 IL2

5 55438580 rs6859219 100E+00 ANKRD55

5 102608924 rs2561477 936E-01 GIN1

6 106568034 rs548234 180E-04 PRDM1

6 138002637 rs10499194 212E-04 TNFAIP3

6 159482521 rs394581 162E-05 TAGAP

6 167540842 rs1571878 426E-07 CCR6

7 128594183 rs10488631 326E-04 IRF5

8 11343973 rs2736340 259E-02 BLK

9 34743681 rs951005 960E-06 CCL21

9 123640500 rs1953126 208E-06 TRAF1

10 6099045 rs2104286 441E-10 IL2RA

10 6393260 rs4750316 422E-08 PRKCQ

10 8095340 rs2275806 726E-05 GATA3

10 63800004 rs12764378 884E-01 ARID5B

11 36525293 rs540386 671E-11 RAG1

11 60909581 rs595158 399E-11 CD5

11 118611781 rs10892279 919E-01 DDX6

12 57968715 rs1678542 658E-01 B4GALNT1

15 38828140 rs8043085 682E-08 RASGRP1

15 69991417 rs8026898 943E-01 KIF23

16 86019087 rs13330176 300E-07 IRF8

17 38040763 rs2872507 247E-05 IKZF3

19 10295433 rs4804493 751E-01 DNMT1


20 44734310 rs6032662 438E-10 CD40

21 35911599 rs2834512 197E-01 RCAN1

21 36715761 rs9979383 914E-02 RUNX1

21 43836186 rs11203203 106E-01 UBASH3A

22 21982892 rs2298428 964E-01 YDJC

22 37544810 rs3218253 100E-08 IL2RB





1-SNP model

Haplotypic risk

SNP alleles

(Mm)


(Mm)



AG 072 126

GG 023 143

GA 00002 -


CG 006 117

AA 023 118

AG 001 139

2p16-p15


AG 058 12

GG 038 136

GA 0005 -


AT 024 115

CA 006 120

AA 0 -


AG 021 118

GA 002 137

AA 002 155


CC 009 085

GA 004 062

GC 0 -



Chr POS Gene region

Lead SNP Low MAF

SNP

MAF

UNAFF

MAF

AFF

P OR r2

to lead

Location REG POT7X

CONS 17WA

Y


2 61391558 REL rs17008218 005 004 439E-05 083 1 INTRONIC 000 008

2 61581489 REL rs17009924 005 004 947E-05 084 092 INTRONIC 000 000

















GWAS IMMUNOCHIP


P OR

rs13315591a PXK 3 009 46x10-8 129 rs35677470 008 17 X 10-07 119 028 103 027 058

rs10488631 IRF5 7 011 42x10-11 119 rs3807306 049 19 X 10-07 089 18 X 10-05 11 02 1

rs934734 SPRED2 2 049 53x10-10 113 rs6546146 038 80 X 10-07 09 30 X 10-04 107 053 095

rs3761847 TRAF1 9 043 21x10-7 113 rs10739580 033 17 X 10-06 112 17 X 10-04 107 074 1

rs2104286 IL2RA 10 027 2x10-3 092 rs10795791 04 30 X 10-06 109 10 X 10-04 091 025 1

rs11586238 CD2 1 024 1x10-5 113 rs798000 034 62 X 10-06 111 30 X 10-03 107 033 072

rs10919563 PTPRC 1 013 2x10-4 088 rs2014863 036 21 X 10-05 109 77 X 10-04 091 007 1

rs1678542 KIF5A 12 038 2x10-4 091 rs10683701 033 23 X 10-05 09 10 X 10-03 093 027 058

rs548234 PRDM1 6 033 97x10-5 11 rs6911690 012 12 X 10-04 087 002 104 01 1

rs6822844 IL2-IL21 4 018 7x10-4 09 rs78560100 007 58 X 10-04 113 001 094 002 1

rs540386b TRAF6 11 014 3x10-4 088 rs570676 038 21 X 10-03 093 007 095 018 1




Region size


Region size


LD SNPS (ns)

r2gt09




PTPN22 1p13 113863087-

114527968

665kb

rs2476601b 114303808-114377568



ANKRD55 5q11 55414956-

55447909

33kb

rs71624119a 55440730-55442249


TNFAIP3 6q23 137896596-

138125335

229kb

rs6920220b 137959235-138006504

4727kb 761 (0) 9 (0) 18185kb 5 of TNFAIP3

TNFAIP3 6q23 137896596-

138125335

229kb

rs58721818g 138178293-

138243739

6545kb 835 (38) 7 (0) TNFAIP3

RBPJ 4p15 26028805-

26134465

106kb

rs932036a 26085480-26128710

4323kb 486 (0) 25 (0) 3637kb 5 of RBPJ

CCR6 6q27 167355854-

167547954

192kb

rs59466457b 167526096-

167540842

1475kb 234 (0) 6 (0) Intron 1 of CCR6

STAT4 2q32 191873553-

192007734

134kb

rs13426947a 191900449-191935804


STAT4 2q32 191873553- 134kb rs932169e 191929278-191929278



192007734

CCL21 9p13 34649442-

34974974

325kb rs2812378b 34707373-34710338

297kb 41 (4) 3 (0) CCL21

CD40 20q13 44594228-

44784336

190kb

rs6032662b 44730245-44747947


MMEL1 1p36 2406888-

2785671

378kb

rs2843401b 2516781-2709164

19238kb

4571 (73)

85 (1)


AFF3 2q11 100544954-

101038647

493kb

rs10209110a 100640432-100730111


REL 2p16 60914729-

61864047

949kb

rs34695944b 61072664-61164331

9167kb 876 (18) 14 (0) Complete REL

REL 2p16 60914729-

61864047

949kb

rs78404002g 61466603-61776131

30953kb

3579 (24)

5 (0)


USP34 SNORA70B XPO1

31596kb 3 of REL CTLA4 2q33 204678417-

204816382

138kb

rs11571302b 204738919-204745003


GIN1 5q21 102098582-

102711659

613kb

rs39984a 102595778-102625335

2956kb

385 (7)

40 (0)


13992kb 5of GIN1

PXK 3p14 58154177-

58549297

395kb

rs35677470a 58181499-58183636


13497kb 5 of PXK

IRF5 7q32 128549568- 228kb rs3807306b 128580680-128580680



128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884


SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300


TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485


CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)


CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515



PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































20 44734310 rs6032662 438E-10 CD40

21 35911599 rs2834512 197E-01 RCAN1

21 36715761 rs9979383 914E-02 RUNX1

21 43836186 rs11203203 106E-01 UBASH3A

22 21982892 rs2298428 964E-01 YDJC

22 37544810 rs3218253 100E-08 IL2RB





1-SNP model

Haplotypic risk

SNP alleles

(Mm)


(Mm)



AG 072 126

GG 023 143

GA 00002 -


CG 006 117

AA 023 118

AG 001 139

2p16-p15


AG 058 12

GG 038 136

GA 0005 -


AT 024 115

CA 006 120

AA 0 -


AG 021 118

GA 002 137

AA 002 155


CC 009 085

GA 004 062

GC 0 -



Chr POS Gene region

Lead SNP Low MAF

SNP

MAF

UNAFF

MAF

AFF

P OR r2

to lead

Location REG POT7X

CONS 17WA

Y


2 61391558 REL rs17008218 005 004 439E-05 083 1 INTRONIC 000 008

2 61581489 REL rs17009924 005 004 947E-05 084 092 INTRONIC 000 000

















GWAS IMMUNOCHIP


P OR

rs13315591a PXK 3 009 46x10-8 129 rs35677470 008 17 X 10-07 119 028 103 027 058

rs10488631 IRF5 7 011 42x10-11 119 rs3807306 049 19 X 10-07 089 18 X 10-05 11 02 1

rs934734 SPRED2 2 049 53x10-10 113 rs6546146 038 80 X 10-07 09 30 X 10-04 107 053 095

rs3761847 TRAF1 9 043 21x10-7 113 rs10739580 033 17 X 10-06 112 17 X 10-04 107 074 1

rs2104286 IL2RA 10 027 2x10-3 092 rs10795791 04 30 X 10-06 109 10 X 10-04 091 025 1

rs11586238 CD2 1 024 1x10-5 113 rs798000 034 62 X 10-06 111 30 X 10-03 107 033 072

rs10919563 PTPRC 1 013 2x10-4 088 rs2014863 036 21 X 10-05 109 77 X 10-04 091 007 1

rs1678542 KIF5A 12 038 2x10-4 091 rs10683701 033 23 X 10-05 09 10 X 10-03 093 027 058

rs548234 PRDM1 6 033 97x10-5 11 rs6911690 012 12 X 10-04 087 002 104 01 1

rs6822844 IL2-IL21 4 018 7x10-4 09 rs78560100 007 58 X 10-04 113 001 094 002 1

rs540386b TRAF6 11 014 3x10-4 088 rs570676 038 21 X 10-03 093 007 095 018 1




Region size


Region size


LD SNPS (ns)

r2gt09




PTPN22 1p13 113863087-

114527968

665kb

rs2476601b 114303808-114377568



ANKRD55 5q11 55414956-

55447909

33kb

rs71624119a 55440730-55442249


TNFAIP3 6q23 137896596-

138125335

229kb

rs6920220b 137959235-138006504

4727kb 761 (0) 9 (0) 18185kb 5 of TNFAIP3

TNFAIP3 6q23 137896596-

138125335

229kb

rs58721818g 138178293-

138243739

6545kb 835 (38) 7 (0) TNFAIP3

RBPJ 4p15 26028805-

26134465

106kb

rs932036a 26085480-26128710

4323kb 486 (0) 25 (0) 3637kb 5 of RBPJ

CCR6 6q27 167355854-

167547954

192kb

rs59466457b 167526096-

167540842

1475kb 234 (0) 6 (0) Intron 1 of CCR6

STAT4 2q32 191873553-

192007734

134kb

rs13426947a 191900449-191935804


STAT4 2q32 191873553- 134kb rs932169e 191929278-191929278



192007734

CCL21 9p13 34649442-

34974974

325kb rs2812378b 34707373-34710338

297kb 41 (4) 3 (0) CCL21

CD40 20q13 44594228-

44784336

190kb

rs6032662b 44730245-44747947


MMEL1 1p36 2406888-

2785671

378kb

rs2843401b 2516781-2709164

19238kb

4571 (73)

85 (1)


AFF3 2q11 100544954-

101038647

493kb

rs10209110a 100640432-100730111


REL 2p16 60914729-

61864047

949kb

rs34695944b 61072664-61164331

9167kb 876 (18) 14 (0) Complete REL

REL 2p16 60914729-

61864047

949kb

rs78404002g 61466603-61776131

30953kb

3579 (24)

5 (0)


USP34 SNORA70B XPO1

31596kb 3 of REL CTLA4 2q33 204678417-

204816382

138kb

rs11571302b 204738919-204745003


GIN1 5q21 102098582-

102711659

613kb

rs39984a 102595778-102625335

2956kb

385 (7)

40 (0)


13992kb 5of GIN1

PXK 3p14 58154177-

58549297

395kb

rs35677470a 58181499-58183636


13497kb 5 of PXK

IRF5 7q32 128549568- 228kb rs3807306b 128580680-128580680



128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884


SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300


TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485


CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)


CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515



PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40



















































1-SNP model

Haplotypic risk

SNP alleles

(Mm)


(Mm)



AG 072 126

GG 023 143

GA 00002 -


CG 006 117

AA 023 118

AG 001 139

2p16-p15


AG 058 12

GG 038 136

GA 0005 -


AT 024 115

CA 006 120

AA 0 -


AG 021 118

GA 002 137

AA 002 155


CC 009 085

GA 004 062

GC 0 -



Chr POS Gene region

Lead SNP Low MAF

SNP

MAF

UNAFF

MAF

AFF

P OR r2

to lead

Location REG POT7X

CONS 17WA

Y


2 61391558 REL rs17008218 005 004 439E-05 083 1 INTRONIC 000 008

2 61581489 REL rs17009924 005 004 947E-05 084 092 INTRONIC 000 000

















GWAS IMMUNOCHIP


P OR

rs13315591a PXK 3 009 46x10-8 129 rs35677470 008 17 X 10-07 119 028 103 027 058

rs10488631 IRF5 7 011 42x10-11 119 rs3807306 049 19 X 10-07 089 18 X 10-05 11 02 1

rs934734 SPRED2 2 049 53x10-10 113 rs6546146 038 80 X 10-07 09 30 X 10-04 107 053 095

rs3761847 TRAF1 9 043 21x10-7 113 rs10739580 033 17 X 10-06 112 17 X 10-04 107 074 1

rs2104286 IL2RA 10 027 2x10-3 092 rs10795791 04 30 X 10-06 109 10 X 10-04 091 025 1

rs11586238 CD2 1 024 1x10-5 113 rs798000 034 62 X 10-06 111 30 X 10-03 107 033 072

rs10919563 PTPRC 1 013 2x10-4 088 rs2014863 036 21 X 10-05 109 77 X 10-04 091 007 1

rs1678542 KIF5A 12 038 2x10-4 091 rs10683701 033 23 X 10-05 09 10 X 10-03 093 027 058

rs548234 PRDM1 6 033 97x10-5 11 rs6911690 012 12 X 10-04 087 002 104 01 1

rs6822844 IL2-IL21 4 018 7x10-4 09 rs78560100 007 58 X 10-04 113 001 094 002 1

rs540386b TRAF6 11 014 3x10-4 088 rs570676 038 21 X 10-03 093 007 095 018 1




Region size


Region size


LD SNPS (ns)

r2gt09




PTPN22 1p13 113863087-

114527968

665kb

rs2476601b 114303808-114377568



ANKRD55 5q11 55414956-

55447909

33kb

rs71624119a 55440730-55442249


TNFAIP3 6q23 137896596-

138125335

229kb

rs6920220b 137959235-138006504

4727kb 761 (0) 9 (0) 18185kb 5 of TNFAIP3

TNFAIP3 6q23 137896596-

138125335

229kb

rs58721818g 138178293-

138243739

6545kb 835 (38) 7 (0) TNFAIP3

RBPJ 4p15 26028805-

26134465

106kb

rs932036a 26085480-26128710

4323kb 486 (0) 25 (0) 3637kb 5 of RBPJ

CCR6 6q27 167355854-

167547954

192kb

rs59466457b 167526096-

167540842

1475kb 234 (0) 6 (0) Intron 1 of CCR6

STAT4 2q32 191873553-

192007734

134kb

rs13426947a 191900449-191935804


STAT4 2q32 191873553- 134kb rs932169e 191929278-191929278



192007734

CCL21 9p13 34649442-

34974974

325kb rs2812378b 34707373-34710338

297kb 41 (4) 3 (0) CCL21

CD40 20q13 44594228-

44784336

190kb

rs6032662b 44730245-44747947


MMEL1 1p36 2406888-

2785671

378kb

rs2843401b 2516781-2709164

19238kb

4571 (73)

85 (1)


AFF3 2q11 100544954-

101038647

493kb

rs10209110a 100640432-100730111


REL 2p16 60914729-

61864047

949kb

rs34695944b 61072664-61164331

9167kb 876 (18) 14 (0) Complete REL

REL 2p16 60914729-

61864047

949kb

rs78404002g 61466603-61776131

30953kb

3579 (24)

5 (0)


USP34 SNORA70B XPO1

31596kb 3 of REL CTLA4 2q33 204678417-

204816382

138kb

rs11571302b 204738919-204745003


GIN1 5q21 102098582-

102711659

613kb

rs39984a 102595778-102625335

2956kb

385 (7)

40 (0)


13992kb 5of GIN1

PXK 3p14 58154177-

58549297

395kb

rs35677470a 58181499-58183636


13497kb 5 of PXK

IRF5 7q32 128549568- 228kb rs3807306b 128580680-128580680



128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884


SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300


TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485


CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)


CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515



PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































Chr POS Gene region

Lead SNP Low MAF

SNP

MAF

UNAFF

MAF

AFF

P OR r2

to lead

Location REG POT7X

CONS 17WA

Y


2 61391558 REL rs17008218 005 004 439E-05 083 1 INTRONIC 000 008

2 61581489 REL rs17009924 005 004 947E-05 084 092 INTRONIC 000 000

















GWAS IMMUNOCHIP


P OR

rs13315591a PXK 3 009 46x10-8 129 rs35677470 008 17 X 10-07 119 028 103 027 058

rs10488631 IRF5 7 011 42x10-11 119 rs3807306 049 19 X 10-07 089 18 X 10-05 11 02 1

rs934734 SPRED2 2 049 53x10-10 113 rs6546146 038 80 X 10-07 09 30 X 10-04 107 053 095

rs3761847 TRAF1 9 043 21x10-7 113 rs10739580 033 17 X 10-06 112 17 X 10-04 107 074 1

rs2104286 IL2RA 10 027 2x10-3 092 rs10795791 04 30 X 10-06 109 10 X 10-04 091 025 1

rs11586238 CD2 1 024 1x10-5 113 rs798000 034 62 X 10-06 111 30 X 10-03 107 033 072

rs10919563 PTPRC 1 013 2x10-4 088 rs2014863 036 21 X 10-05 109 77 X 10-04 091 007 1

rs1678542 KIF5A 12 038 2x10-4 091 rs10683701 033 23 X 10-05 09 10 X 10-03 093 027 058

rs548234 PRDM1 6 033 97x10-5 11 rs6911690 012 12 X 10-04 087 002 104 01 1

rs6822844 IL2-IL21 4 018 7x10-4 09 rs78560100 007 58 X 10-04 113 001 094 002 1

rs540386b TRAF6 11 014 3x10-4 088 rs570676 038 21 X 10-03 093 007 095 018 1




Region size


Region size


LD SNPS (ns)

r2gt09




PTPN22 1p13 113863087-

114527968

665kb

rs2476601b 114303808-114377568



ANKRD55 5q11 55414956-

55447909

33kb

rs71624119a 55440730-55442249


TNFAIP3 6q23 137896596-

138125335

229kb

rs6920220b 137959235-138006504

4727kb 761 (0) 9 (0) 18185kb 5 of TNFAIP3

TNFAIP3 6q23 137896596-

138125335

229kb

rs58721818g 138178293-

138243739

6545kb 835 (38) 7 (0) TNFAIP3

RBPJ 4p15 26028805-

26134465

106kb

rs932036a 26085480-26128710

4323kb 486 (0) 25 (0) 3637kb 5 of RBPJ

CCR6 6q27 167355854-

167547954

192kb

rs59466457b 167526096-

167540842

1475kb 234 (0) 6 (0) Intron 1 of CCR6

STAT4 2q32 191873553-

192007734

134kb

rs13426947a 191900449-191935804


STAT4 2q32 191873553- 134kb rs932169e 191929278-191929278



192007734

CCL21 9p13 34649442-

34974974

325kb rs2812378b 34707373-34710338

297kb 41 (4) 3 (0) CCL21

CD40 20q13 44594228-

44784336

190kb

rs6032662b 44730245-44747947


MMEL1 1p36 2406888-

2785671

378kb

rs2843401b 2516781-2709164

19238kb

4571 (73)

85 (1)


AFF3 2q11 100544954-

101038647

493kb

rs10209110a 100640432-100730111


REL 2p16 60914729-

61864047

949kb

rs34695944b 61072664-61164331

9167kb 876 (18) 14 (0) Complete REL

REL 2p16 60914729-

61864047

949kb

rs78404002g 61466603-61776131

30953kb

3579 (24)

5 (0)


USP34 SNORA70B XPO1

31596kb 3 of REL CTLA4 2q33 204678417-

204816382

138kb

rs11571302b 204738919-204745003


GIN1 5q21 102098582-

102711659

613kb

rs39984a 102595778-102625335

2956kb

385 (7)

40 (0)


13992kb 5of GIN1

PXK 3p14 58154177-

58549297

395kb

rs35677470a 58181499-58183636


13497kb 5 of PXK

IRF5 7q32 128549568- 228kb rs3807306b 128580680-128580680



128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884


SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300


TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485


CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)


CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515



PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40





















































GWAS IMMUNOCHIP


P OR

rs13315591a PXK 3 009 46x10-8 129 rs35677470 008 17 X 10-07 119 028 103 027 058

rs10488631 IRF5 7 011 42x10-11 119 rs3807306 049 19 X 10-07 089 18 X 10-05 11 02 1

rs934734 SPRED2 2 049 53x10-10 113 rs6546146 038 80 X 10-07 09 30 X 10-04 107 053 095

rs3761847 TRAF1 9 043 21x10-7 113 rs10739580 033 17 X 10-06 112 17 X 10-04 107 074 1

rs2104286 IL2RA 10 027 2x10-3 092 rs10795791 04 30 X 10-06 109 10 X 10-04 091 025 1

rs11586238 CD2 1 024 1x10-5 113 rs798000 034 62 X 10-06 111 30 X 10-03 107 033 072

rs10919563 PTPRC 1 013 2x10-4 088 rs2014863 036 21 X 10-05 109 77 X 10-04 091 007 1

rs1678542 KIF5A 12 038 2x10-4 091 rs10683701 033 23 X 10-05 09 10 X 10-03 093 027 058

rs548234 PRDM1 6 033 97x10-5 11 rs6911690 012 12 X 10-04 087 002 104 01 1

rs6822844 IL2-IL21 4 018 7x10-4 09 rs78560100 007 58 X 10-04 113 001 094 002 1

rs540386b TRAF6 11 014 3x10-4 088 rs570676 038 21 X 10-03 093 007 095 018 1




Region size


Region size


LD SNPS (ns)

r2gt09




PTPN22 1p13 113863087-

114527968

665kb

rs2476601b 114303808-114377568



ANKRD55 5q11 55414956-

55447909

33kb

rs71624119a 55440730-55442249


TNFAIP3 6q23 137896596-

138125335

229kb

rs6920220b 137959235-138006504

4727kb 761 (0) 9 (0) 18185kb 5 of TNFAIP3

TNFAIP3 6q23 137896596-

138125335

229kb

rs58721818g 138178293-

138243739

6545kb 835 (38) 7 (0) TNFAIP3

RBPJ 4p15 26028805-

26134465

106kb

rs932036a 26085480-26128710

4323kb 486 (0) 25 (0) 3637kb 5 of RBPJ

CCR6 6q27 167355854-

167547954

192kb

rs59466457b 167526096-

167540842

1475kb 234 (0) 6 (0) Intron 1 of CCR6

STAT4 2q32 191873553-

192007734

134kb

rs13426947a 191900449-191935804


STAT4 2q32 191873553- 134kb rs932169e 191929278-191929278



192007734

CCL21 9p13 34649442-

34974974

325kb rs2812378b 34707373-34710338

297kb 41 (4) 3 (0) CCL21

CD40 20q13 44594228-

44784336

190kb

rs6032662b 44730245-44747947


MMEL1 1p36 2406888-

2785671

378kb

rs2843401b 2516781-2709164

19238kb

4571 (73)

85 (1)


AFF3 2q11 100544954-

101038647

493kb

rs10209110a 100640432-100730111


REL 2p16 60914729-

61864047

949kb

rs34695944b 61072664-61164331

9167kb 876 (18) 14 (0) Complete REL

REL 2p16 60914729-

61864047

949kb

rs78404002g 61466603-61776131

30953kb

3579 (24)

5 (0)


USP34 SNORA70B XPO1

31596kb 3 of REL CTLA4 2q33 204678417-

204816382

138kb

rs11571302b 204738919-204745003


GIN1 5q21 102098582-

102711659

613kb

rs39984a 102595778-102625335

2956kb

385 (7)

40 (0)


13992kb 5of GIN1

PXK 3p14 58154177-

58549297

395kb

rs35677470a 58181499-58183636


13497kb 5 of PXK

IRF5 7q32 128549568- 228kb rs3807306b 128580680-128580680



128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884


SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300


TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485


CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)


CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515



PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40




















































Region size


Region size


LD SNPS (ns)

r2gt09




PTPN22 1p13 113863087-

114527968

665kb

rs2476601b 114303808-114377568



ANKRD55 5q11 55414956-

55447909

33kb

rs71624119a 55440730-55442249


TNFAIP3 6q23 137896596-

138125335

229kb

rs6920220b 137959235-138006504

4727kb 761 (0) 9 (0) 18185kb 5 of TNFAIP3

TNFAIP3 6q23 137896596-

138125335

229kb

rs58721818g 138178293-

138243739

6545kb 835 (38) 7 (0) TNFAIP3

RBPJ 4p15 26028805-

26134465

106kb

rs932036a 26085480-26128710

4323kb 486 (0) 25 (0) 3637kb 5 of RBPJ

CCR6 6q27 167355854-

167547954

192kb

rs59466457b 167526096-

167540842

1475kb 234 (0) 6 (0) Intron 1 of CCR6

STAT4 2q32 191873553-

192007734

134kb

rs13426947a 191900449-191935804


STAT4 2q32 191873553- 134kb rs932169e 191929278-191929278



192007734

CCL21 9p13 34649442-

34974974

325kb rs2812378b 34707373-34710338

297kb 41 (4) 3 (0) CCL21

CD40 20q13 44594228-

44784336

190kb

rs6032662b 44730245-44747947


MMEL1 1p36 2406888-

2785671

378kb

rs2843401b 2516781-2709164

19238kb

4571 (73)

85 (1)


AFF3 2q11 100544954-

101038647

493kb

rs10209110a 100640432-100730111


REL 2p16 60914729-

61864047

949kb

rs34695944b 61072664-61164331

9167kb 876 (18) 14 (0) Complete REL

REL 2p16 60914729-

61864047

949kb

rs78404002g 61466603-61776131

30953kb

3579 (24)

5 (0)


USP34 SNORA70B XPO1

31596kb 3 of REL CTLA4 2q33 204678417-

204816382

138kb

rs11571302b 204738919-204745003


GIN1 5q21 102098582-

102711659

613kb

rs39984a 102595778-102625335

2956kb

385 (7)

40 (0)


13992kb 5of GIN1

PXK 3p14 58154177-

58549297

395kb

rs35677470a 58181499-58183636


13497kb 5 of PXK

IRF5 7q32 128549568- 228kb rs3807306b 128580680-128580680



128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884


SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300


TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485


CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)


CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515



PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































192007734

CCL21 9p13 34649442-

34974974

325kb rs2812378b 34707373-34710338

297kb 41 (4) 3 (0) CCL21

CD40 20q13 44594228-

44784336

190kb

rs6032662b 44730245-44747947


MMEL1 1p36 2406888-

2785671

378kb

rs2843401b 2516781-2709164

19238kb

4571 (73)

85 (1)


AFF3 2q11 100544954-

101038647

493kb

rs10209110a 100640432-100730111


REL 2p16 60914729-

61864047

949kb

rs34695944b 61072664-61164331

9167kb 876 (18) 14 (0) Complete REL

REL 2p16 60914729-

61864047

949kb

rs78404002g 61466603-61776131

30953kb

3579 (24)

5 (0)


USP34 SNORA70B XPO1

31596kb 3 of REL CTLA4 2q33 204678417-

204816382

138kb

rs11571302b 204738919-204745003


GIN1 5q21 102098582-

102711659

613kb

rs39984a 102595778-102625335

2956kb

385 (7)

40 (0)


13992kb 5of GIN1

PXK 3p14 58154177-

58549297

395kb

rs35677470a 58181499-58183636


13497kb 5 of PXK

IRF5 7q32 128549568- 228kb rs3807306b 128580680-128580680



128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884


SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300


TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485


CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)


CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515



PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































128777520

IL2RB 22q12 37537514-

37562111

24kb rs3218251b 37544245-37545505

126kb 24 (0) 5 (0) Intron 1 of IL2RB

DDX6 11q23 118341921-

118765600

423kb

rs4938573b 118662993-118745884


SPRED2 2p14 65397595-

65717094

319kb

rs6546146b 65556324-65598300


TAGAP 6q25 159340939-

159541830

201kb

rs629326b 159489791-159496713

692kb

90 (0)

3 (0)

2361kb 5 of TAGAP

TRAF1 9q33 123351121-

124131512

780kb rs10739580b 123640500-123708286

6779kb 920 (21) 75 (0) Complete TRAF1

IL2RA 10p15 6030243-

6161781

131kb

rs10795791a 6106266-6108340

208kb 29 (0) 4 (0) 193kb 5 of IL2RA

BLK 8p23 11285384-

11414013

128kb

rs4840565a 11338383-11352485


CD2 1p13 117231902-

117299420

67kb

rs798000b 117280696-117280696

1bp 2 (0) 1 (0) 1631kb 5 of CD2

CD28 2q33 204446380-

204690355

244kb

rs1980422f 204610004-204634569

2457kb

314 (0)

7 (0)


CD28 2q33 204446380-

204690355

244kb rs55686954 204586515-204586515



PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































PTPRC 1q31 197311228-

197938330

627kb

rs2014863a 198791907-198810008

1810kb 175 (0) 6 (0) 6536kb 3 of PTPRC

KIF5A 12q13 57626582-

58124534

497kb rs10683701b 58034835-58105094


5442kb 3 of KIF5A

PRKCQ 10p15 6388071-

6545104

157kb

rs947474a 6390450-6390450

1bp 1 (0) 1 (0) 7866kb 3 of PRKCQ

FCGR2A 1q23 161282384-

161679644

397kb

rs10494360b 161463876-161480649


PRDM1 6q21 106532756-

106627910

95kb

rs6911690b 106435981-106508640

7266kb 831 (0) 59 (0) 2555kb 5 of PRDM1

IL2-IL21 4q27 122982314-

123565302

583kb

rs78560100a 123030583-123503591

47301kb

5420 (73) 119 (0)

KIAA1109ADAD1IL2

3019kb 3 of IL21

TRAF6 11p12 rs570676b 36486064-36519624



TYK2 19p13 10396336-

10628468

232kb

rs34536443b 10427721-10492274


complete TYK2

TYK2 19p13 10396336-

10628468

232kb rs3176767g 10446897-10449778


IRAK1 Xq28 153170618-

154445759

1275kb

rs13397b 153196345-153248248




TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































TLE3 15q23 rs8026898b 69984462-70010647

2619kb 376 (0) 6 (0) 32948kb 3 of TLE3

RASGRP1 15q14 38814377-

38972177

157kb

rs8043085b 38828140-38844106

1597kb

192 (0)

4 (0)

Intron 2 of RASGRP1

RASGRP1 15q14 38814377-

38972177

157kb

rs77397211f 38970496-38970496

1bp 1 (0) 1 (0) 11272kb 5 of RASGRP1

PADI4 1p36 17597181-

17679598

82kb

rs2240336b 17673102-17674402

130kb 19 (0) 3 (0) Intron 9 PADI4

IL6R 1q21 155019710-

156045183

1025kb

rs8192284a

(rs2228145) 154418749-154428283


IRF8 16q24 85993580-

86024104

30kb

rs13330176b 86016026-86019087

306kb 56 (0) 4 (0) 5983kb 3 of IRF8


ARID5B 10q21 rs12764378d 63786554-63800004

1345kb

164 (0)

4 (0)

Intron 4 of ARID5B

RUNX1 21q22 rs9979383c 36712588-36715761

317kb 62 (0) 3 (0) 5 region of RUNX1

IKZF3 17q12 37382674-

38240216

857kb rs12936409rs2872507c

37912377-38080912


16492kb 3 of ORMDL3

POU3F1 1p34 rs883220d 38614867-38644861

3000kb 427 (0) 9 (0) 10242kb 5 of POU3F1

RCAN1 21q22 rs2834512d 35909625-35930915

2129kb 370 (0) 13 (0) Intron 1 of RCAN1




GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40



















































GATA3 10p14 rs2275806d 8095340-8097368









Immunochip



MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40



















































MAF




rs6032662 CD40 rs1883832 20 44180389 100 5rsquo UTR 0486 0000 026































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40





























































MMEL rs2843401 FCGR2A rs11810143 173E-05 4297

PRKCQ rs947474 GATA3 rs2275806 833E-05 3935

PTPN22 rs2476601 RBPJ rs12506688 144E-04 3802

PADI4 rs2240336 TAGAP rs629326 326E-04 3594

ANKRD55 rs71624119 TRAF6 rs570676 476E-04 3494




Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































Gene Top variant(s)

Celiac disease

MAF P

Celiac

OR

Celiac

Top Variant(s)

RA

MAF P

RA

OR

RA

P for Celiac

SNP in

RA iChip

OR for Celiac

SNP in RA

iChip

r2 Drsquo


-9 087 16x10

-5 092 088 096

RELPUS10a rs13003464 039 43x10

-16 117 rs34695944

rs78404002

037

005

26x10-8

34x10-5

113

085

05 099 002

006

016

1


rs932169b

019

009

72x10-10

66x10-6

115

116

35x10-4

086 002

0004

1

1


rs932169b

019

009

72x10-10

66x10-6

115

116

13x10-3

107 015

001

045

034


rs932169b

019

009

72x10-10

66x10-6

115

116

5x10-3

092 003

0005

1

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

87x10-6

111 0006

1

014

1


rs1980422b

048

023

45x10-8

87x10-6

089

112

16x10-3

093 021

0

1

002


rs1980422b

048

023

45x10-8

87x10-6

089

112

08 101 005

001

1

1


-4 113 001 094 002 099


113 9x10-4

112 1 1


-7 113 78x10

-3 105 02 086


rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-10

115 1

003

1

047


rs77027760

019 21 times 10minus7 088 rs6920220a

rs58721818b

02

003

23x10-13

12x10-8

12

138

24x10-4

091 005 0007

1 1


-6 09 002 097 044 069


09 03 097 006 1


ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































ELMO1b [1kg_7_ 37384979]

rs79758729

010 21 times 10minus8 118 rs75351767 010 29x10-7

116 91x10-7

115 098 099


-5 088 005 096 002 019


rs569158b

017 018

25x10-5

32x10-4

09

11

47x10-4

092 075 0008

1 036


-7 087 15x10

-4 091 062 088


-6 122 1x10

-4 11 0008 1


122 45x10-6

122 1 1


-12 123 1 1



SNP Study P-



rs34536443 230E-14 276E-14 900E-15

rs13397 120E-12 148E-10 120E-12

rs8026898 140E-10 169E-10 430E-11

rs8043085 140E-10 172E-10 110E-10

rs2240336 590E-09 727E-09 217E-08

rs8192284 130E-08 162E-08 720E-08

rs13330176 400E-08 495E-08 405E-08








0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40























































0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40





















































0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40



















































0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2843401

01

03

05

07

09

r2

PLCH2

PANK4

HES5

LOC115110

TNFRSF14

C1orf93

MMEL1



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2240336

01

03

05

07

09

r2

PADI3 PADI4 PADI6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs883220

01

03

05

07

09

r2

FHL3

UTP11L

POU3F1



0

20

40

60

80

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2476601

01

03

05

07

09

r2

MAGI3

PHTF1

RSBN1

PTPN22

BCL2L15

AP4B1

DCLRE1B

HIPK1

SYT6



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs798000

01

03

05

07

09

r2

CD58

IGSF3

MIR320B1 CD2 PTGFRN

CD101

TTF2

MIR942

TRIM45


chr1152619326minus152756082 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8192284

01

03

05

07

09

r2

IL6R SHE

TDRD10



chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































chr1159513289minus160026465 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11810143

01

03

05

07

09

r2

PCP4L1

MPZ

SDHC

LOC642502

C1orf192 FCGR2A

HSPA6

FCGR3A

FCGR2C

HSPA7

FCGR3B

FCGR2B

RPL31P11

FCRLA

FCRLB

DUSP12

ATF6


chr1196638288minus197276449 (pos)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs16843807

01

03

05

07

09

r2


MIR181A1



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34695944

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78404002

01

03

05

07

09

r2

BCL11A PAPOLG

REL

PUS10

PEX13

KIAA1841

C2orf74

AHSA2

USP34

SNORA70B

XPO1

FAM161A



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6546146

01

03

05

07

09

r2

RAB1A ACTR2 SPRED2


chr299408345minus101152002 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10209110

01

03

05

07

09

r2

REV1

AFF3

LONRF2

CHST10

NMS

PDCL3

NPAS2

RPL31

TBC1D8



chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































chr2191545035minus191735211 (all)

0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13426947

01

03

05

07

09

r2

STAT1 STAT4


chr2191545035minus191735211 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3024921

01

03

05

07

09

r2

STAT1 STAT4



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs11571302

01

03

05

07

09

r2

CTLA4 ICOS



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs1980422

01

03

05

07

09

r2

CD28



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs55686954

01

03

05

07

09

r2

CD28


chr358121307minus58547932 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs35677470

01

03

05

07

09

r2

FLNB

DNASE1L3

ABHD6

RPP14

PXK

PDHB

KCTD6

ACOX2

FAM107A




0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40



















































0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12506688

01

03

05

07

09

r2


chr4123057351minus123910137 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs78560100

01

03

05

07

09

r2

TRPC3 KIAA1109

ADAD1

IL2 IL21 LOC729338

BBS12


chr555439092minus55506618 (all)

0

5

10

15

20

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs71624119

01

03

05

07

09

r2

ANKRD55


chr5102117809minus102772349 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs39984

01

03

05

07

09

r2

PAM GIN1

PPIP5K2

C5orf30



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6911690

01

03

05

07

09

r2

PRDM1 ATG5



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6920220

01

03

05

07

09

r2

TNFAIP3




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40



















































0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs58721818

01

03

05

07

09

r2

TNFAIP3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs629326

01

03

05

07

09

r2

RSPH3 TAGAP



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs59466457

01

03

05

07

09

r2


TCP10L2



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3807306

01

03

05

07

09

r2

KCP IRF5 TNPO3

LOC286016

LOC407835

TSPAN33


chr810631365minus11581383 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4840565

01

03

05

07

09

r2

PINX1

MIR1322

XKR6

MIR598

MTMR9

AMAC1L2

TDH

C8orf12

FAM167A

BLK



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2812378

01

03

05

07

09

r2

SIGMAR1

GALT

IL11RA

CCL27

CCL19

CCL21

C9orf144B

C9orf144 KIAA1045

DNAJB5




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40



















































0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10739580

01

03

05

07

09

r2

CDK5RAP2

MEGF9

FBXW2

LOC402377

PSMD5

LOC253039

PHF19

TRAF1

C5 CEP110

RAB14

GSN

STOM


chr106058312minus6332253 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10795791

01

03

05

07

09

r2



chr106417858minus6690270 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs947474

01

03

05

07

09

r2

PRKCQ



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs3802604

01

03

05

07

09

r2

ITIH5 ITIH2

KIN

ATP5C1

TAF3

FLJ45983

GATA3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12764378

01

03

05

07

09

r2

ARID5B



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs570676

01

03

05

07

09

r2


C11orf74



chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































chr1160449767minus60683165 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs595158

01

03

05

07

09

r2

TMEM132A

SLC15A3

CD6 CD5 VPS37C



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs4938573

01

03

05

07

09

r2

MLL

TTC36

TMEM25

C11orf60

ARCN1

PHLDB1

TREH

DDX6 CXCR5

BCL9L



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs10683701

01

03

05

07

09

r2

NXPH4

SHMT2

NDUFA4L2

STAC3

INHBC

INHBE

GLI1

ARHGAP9

MBD6

KIF5A

PIP4K2C

DTX3

GEFT

OS9

AGAP2

LOC100130776

TSPAN31

TSFM

CTDSP2

XRCC6BP1



0

2

4

6

8

10

12

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8043085

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs77397211

01

03

05

07

09

r2

FAM98B

RASGRP1

C15orf53



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs8026898

01

03

05

07

09

r2

KIF23

RPLP1

LOC145837

C15orf50 TLE3

MIR629




0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40



















































0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs13330176

01

03

05

07

09

r2

IRF8


chr1734629978minus35548012 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12936409

01

03

05

07

09

r2

STAC2

LOC90110

FBXL20

MED1

CDK12

NEUROD2

PPP1R1B

STARD3

TCAP

ERBB2

GRB7

IKZF3

ZPBP2

GSDMB

ORMDL3

GSDMA

PSMD3

CSF3

MED24

THRA

NR1D1

MSL1



0

5

10

15

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs34536443

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs12720356

01

03

05

07

09

r2

DNMT1

S1PR2

MRPL4

ICAM1

ICAM4

ICAM5

ZGLP1

ICAM3

TYK2

CDC37

MIR1181

PDE4A KEAP1

S1PR5

ATG4D

MIR1238

KRI1

CDKN2D

SLC44A2

LOC147727

ILF3



0

2

4

6

8

10

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs6032662

01

03

05

07

09

r2

ZNF335 MMP9

SLC12A5

NCOA5 CD40 CDH22



0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs2834512

01

03

05

07

09

r2

KCNE1 RCAN1



chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































chr2135032436minus35761558 (all)

0

2

4

6

8

0

20

40

60

80

100

Recom

bination rate (cMM

b)

rs9979383

01

03

05

07

09

r2

RUNX1

C21orf96




10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40



















































10


10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































10-7

10-6

10-3

001

1

P-va

lue

Cell Types

Tgd

vg2-

24ah

iTh

Tg

dvg

1+vd

6-T

h

Tgd

Th

T4S

P24

-Th

T

4int

8+T

h

T4N

veS

p

T4

Pa

BD

C

T4F

P3+

25+

Sp

T

4S

pB

16

T4M

emS

p

T4M

em44

h62l

Sp

T

4Mem

Tbe

t-S

p

T4M

emT

bet+

Sp

T

4Mem

LN

T

4Mem

44h6

2lL

N

T8S

P69

+Th

T4S

P24

intT

h

TD

PTh

T

4SP

69+

Th

T8S

P24

intT

h

NK

T4+

Lv

01

10-4

10-5





N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40





















































N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40



















































N=50


Yes n=26

No n=24



Yes n=12



No n=12


Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


















































Supplementary Note

Sample collections















































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40






























































consent


(BRAGGSS)


Gerry






R Gorodkin)






Wilkinson)


Saravanan)






Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40






















































Dr S Venkatachalam)







Dahiya)









S K Pathare)




Lynch)





Walker)


Dr E C Rankin)





W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40



















































W S Mitchell)





















Bipolar Disorder






(Newcastle)25







Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40























































Crohns Disease






Hypertension










Worthington40

Type 1 Diabetes



Type 2 Diabetes





Tuberculosis


(Oxford)3




Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40




















































Brown4849



Breast Cancer


Rahman51

Multiple Sclerosis


Gambian Controls









Statistics





Donnelly (Oxford)11







Worthington40


























































































































Documents

Start 196,524 GroupStart 196,524 Chromosome Y 1,735 Mitochondrial 1 Non-polymorphic (all samples) 12,715 Low cluster separation (< 0.4) 12,510 Low call frequency(< 0.98) 2,243