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NTR: a longitudinal twin-family study
Why twins
Not only twins: Multigeneration
An example: ACTION
Netherlands Twin Register• Established around 1987• Recruits new-born twins -> Young NTR• Recruits adolescent / adult twins -> ANTR• Recruits twins, their parents and sibs/spouses/etc
• Surveys, projects, biobank, record linkage
Netherlands Twin Register
grants
NTR history and recruitment
~1989: approach all city councils in the Netherlands
First research project (1983): cardiovascular risk factors in Amsterdam twins and parents
~ 1987: ‘Hello baby’
NTR website, press, Twinfo, via family members, etc.
Number of twin pairs per thousand deliveries
WW2
Average maternal age at birth of children in
Netherlands
Nl Tijdschrift Geneeskunde 2013
NTR participants:where do they live?
Based on 4 digit postal code
Survey collection
Twin studies
Monozygotic (MZ) pairs:(nearly) 100% genetically identical
Dizygotic (DZ) pairs: share on average 50% of segregating genes
heritability = 2(rMZ – rDZ)Genetic Structural Equation modeling
MZ(monozygotic)
DZ (dizygotic)
Add siblings:Increased powerSocial interaction‘twin’ effects
Add parents:Cultural inheritanceAssortmentGE correlation
Aggression scores in MZ (F) twin pairs: twin 1- vs twin 2
Family members resemble each other more than unrelated Ss
MZ twins resemble each other more than DZ twins or sibs
3 yrparentsCBCL‐AD
14 yrselfYSR‐AD
CBCL: Child Behavior Checklist DCB: Devereux Child BehaviorTRF: Teacher Rating Scale (similar items to CBCL)YSR: Youth Self Report (similar items to CBCL)ASR: Adult Self Report (similar items to CBCL)SR: Self Report (early version of YSR and ASR)BDI: Beck Depression Inventory (13 items)HADS: Hospital Anxiety and Depression Scale AD=anxious/depression scaleDCB anxiety = anxiety problemsCIDI =WHO Composite InternationalDiagnostic Interview (in subsample)
7 yrparentsCBCL‐ADteachersTRF‐AD
9/10yrparentsCBCL‐ADteachersTRF‐AD
12 yrparentsCBCL‐ADteachersTRF‐ADself
YSR‐AD
5 yrparentsDCB
Anxiety
YNTRAge 3‐12: both parents on twinsAge 7‐12: teachers on twins and sibsAge 12‐16: self for twins and sibsAge 18: self for twins, sibs, parents
18+ yr (L8)self
ASR‐ADHADS
16 yrselfYSR‐AD
1993 (L2)selfBDI
1995(L3)self
SR‐AD
1997 (L4)self
SR‐AD BDI
2009 (L8)self
ASR‐ADHADS
2000(L5)self
SR‐AD
Same survey
ANTR1991: twins1993: twins , parents1995: twins 1997: twins and sibs2000: twins, sibs, spouses2004/5: twins, sibs, spouses, parents2009/10: twins, sibs, spouses, parents2011: twins, sibs, spouses, parents2013: twins, sibs, spouses, parents2014: twins, sibs, spouses, parents2015: twins, sibs, spouses, parents
Young NTR
Adult NTR2002(L6)self
ASR‐AD
2011 (L9)self
ASR‐AD
1991 (L1)self
SR‐AD
18 yrselfYSR‐AD
Plus CIDIinterviews
2004 (L7)
1 yrmother
2 yrmother
Longitudinal
2013 (L10)self
ASR‐AD
2015L11 and L12
Plus DISCinterviews
2014L11 and L12
European Commission Seventh Framework Programme
The ACTION project:
Aggression in Children: Unraveling gene-environment interplay to inform
Treatment and InterventiON strategies
A collaboration among Scandinavian, English, Australian and Dutch (twin) registers
NTR datasets on Aggression
AGG
ATT
RB
CBCL/YSR/TRF/ASR/OASR Aggression
CBCL/YSR/TRF/ASR Attention problems
CBCL/YSR/TRF/ASR Rule breaking
Young Netherlands Twin Register data
AGG
ATT
RB
Age 3:
M 3
F 3
Age 7:
M 7
F 7T 7
Age 10:
M 10
F 10T 10
Age 12:
M 12
F 12T 12
Age 14:
S 14
Age 16:
S 16
Age 18:
S 18
M 3
F 3
M 7
F 7T 7
M 10
F 10T 10
M 12
F 12T 12
S 14 S 16 S 18
M 3
F 3
M 7
F 7T 7
M 10
F 10T 10
M 12
F 12T 12
S 14 S 16 S 18
Age MEANS AGG-14 items
Males Females
7 4.50 3.33
10 4.05 2.98
12 3.27 2.55
14 3.61 3.49
16 3.22 3.33
18 3.56 3.60
20 2.61 2.78
22 2.24 2.41
Longitudinal Aggression data in Dutch twins(14 items ASEBA)
Argues MeanDemands AttentionDestroys own thingsDestroys others’Gets in fightsAttacks peopleScreams a lotStubborn, sullenMood changesTeases a lotTemperThreatens othersLoud
PF PM
PT1 PT2 PSib
F D E
A
E D F
A
D
F
A
ED
E
A
D
A
E
a a a
aa
e e ed d dd
dd e
1 1 1
1 1e
f f
i
s s
.5 .5 .5 .5 .5 .5
.5 .5 .5
gg
r r1 1 1 1
11
1 1
1
.25
.25.251
0
Genetic or cultural transmission?
If this parameter is significant: evidence for cultural transmission (from Family environment to Phenotype in kids)
Parental generation
Offspring Generation: 2 twins & 1 sibling
Total Survey Biobank ANS DSM Cognition EEG MRIParticipants 200,000 147,041 9,991 4,204 2,554 3,766 1,532 1,230
ANTR surveys 41,800 41,800 9,056 3,446 1,938 2,655 1,316 716YNTR surveys 119,746 119,746 1048 1,308 1,116 2,057 420 774DNA (blood / buccal) 18,791 17,322 9,991 4,048 2,106 3,228 1,208 1,148
NTR Biobank 9,991 9,223 9,991 2,365 805 1,491 828 393GWA Genotyping 12,546 12,096 8,260 1,067 1,545 2,753 946 1,058DNA methylation 3,025 2,956 3,025 1,057 334 602 389 249DNA sequencing 367 347 367 60 31 38 12 10RNA expression 3,370 3,260 3,370 1,270 411 694 488 268RNA sequencing 1,781 1,743 1,781 641 208 396 259 163Metabolomics 5,615 5,482 5,615 47 604 922 561 330Microbiome 276 275 276 1,411 27 39 15 24ANS-function 4,204 3,871 2,365 4,204 868 2,390 810 520DSM-IV interview 2,554 2,546 805 868 2,554 357 219 159Cognition 3,766 3,613 1,491 2,390 357 3,766 1,530 776EEG 1,532 1,474 828 810 219 1,530 1,532 187Brain Imaging 1,230 1,174 393 520 159 776 187 1230
Netherlands Twin Register
Does not reflect longitudinal
DNA, RNA, blood, urine, stool
AutonomicNervousSystem
Psychiatric interviews IQ, not CITO
/ LvS
Brain function & structure
http://www.action‐euproject.eu
Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies
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DNA: epigenetics
Urine: metabolomics
phenotyping
Current data uploads
• DANS (survey data TRF)• dbGaP The database of Genotypes and Phenotypes• European Bioinformatics Institute (EMBL‐EBI)• European Genome‐Phenome Archive (EGA)• MetaboLights
In the next 5 years: create a state of the art repository (NWO‐groot investment)
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