i. Gene-Environment, Gene-Gene Interactionii. Quanto (power calculation)

http://hydra.usc.edu/gxe/

Lab 3

Yu-Chun Jean Yenyyen@hsph.harvard.eduBldg.2 Rm. 200

Sample DatasetYahoo06.dat: a comma delimited file Case-control with 1680 subjects, 16 SNPs

data yahoo;

set yahoo;

/* define genotype scores for snps 5 and 10 */

z5=(a9 eq 3)+(a10 eq 3);

if a9 eq . or a10 eq . then z5=.;

z10=(a19 eq 4)+(a20 eq 4);

if a19 eq . or a20 eq . then z10=.;

run;

/* "interaction tests" assuming linear trend in log OR by SNP5 */

/* Get null -2 log L for "joint test" */

proc logistic data=yahoo;

where z5 ne . and x ne .; *complete case subset;

model d(event='2')=x;

/* Get null -2 log L for "test of statistical interaction" */

proc logistic data=yahoo;

where z5 ne . and x ne .;

model d(event='2')=x z5;

proc logistic data=yahoo;

where z5 ne . and x ne .;

model d(event='2')=x z5 z5*x;

run;

Model -2 log L

Model 1: X only 2212.7

Model 2: X and G5 (multiplicative ORs) 2203.5

Model 3: X, G5 and X*G5 2202.6

Test for SNP5 (adjusted for X): LRT=9.2 on 1 d.f. p=.002(model 2 vs. modle 1)

Test for "statistical interaction" LRT=0.9 on 1 d.f. p=.34(model 3 vs. model 2)

Joint test for G and G-E effects LRT=10.1 on 2 d.f p=.006(model 3 vs. model 1)

/* g-g "interaction" test assuming linear trend in log OR by SNP5 and SNP10 */

proc logistic data=yahoo;

where z5 ne . and z10 ne .;

model d(event='2')=z5 z10 z5*z10;

run;

/* g-g "interaction" test not assuming linear trend in OR by SNP5 and SNP10 */

proc logistic data=yahoo;

where z5 ne . and z10 ne .;

class z5 z10 (ref='0' param=reference);

model d(event='2')=z5 z10 z5*z10;

run;

-1

-0.8

-0.6

-0.4

-0.2

0

0.2

0.4

0.6

0 1 2

SNP5

log

od

ds

Z10=2

Z10=1

Z10=0

/* g-g "interaction" test not assuming linear trend in OR by SNP5 and SNP10 */

data yahoo;

set yahoo;

Z5_Z10=(put(z5, 1.))||(put(z10, 1.));

if z5=. or z10=. then Z5_Z10=' ';

run;

proc freq data=yahoo;

tables z5_z10*z5*z10 / list;

run;

proc logistic data=yahoo;

where z5 ne . and z10 ne .;

class z5_z10 (ref='00' param=reference);

model d(event='2')=z5_z10;

run;

/* fit (constrained) additive interaction between dichotomous g and x */data yahoo; set yahoo; if z5 eq 0 then gcat=0; if z5 gt 0 then gcat=1; if x le .5 and x ne . then xcat=0; if x gt .5 then xcat=1;proc freq data=yahoo; tables gcat*xcat / list;run;proc nlmixed data=yahoo; where gcat ne . and xcat ne .; if (gcat eq 0) and (xcat eq 0) then eta=a; if (gcat eq 0) and (xcat eq 1) then eta=a+b2; if (gcat eq 1) and (xcat eq 0) then eta=a+b1; if (gcat eq 1) and (xcat eq 1) then eta=a+log(exp(b1)+exp(b2)-1); ll = (d=2)*eta - log(1+exp(eta)); model d ~ general(ll); parms a b1 b2=0;run;

Beta_2 is log OR (exposed non carriers)Beta_1 is log OR (carrier unexposed)OR (exposed carrier) is exp(beta_1)+exp(beta_2)-1

/* unconstrained model (to test for departure from additive--risk scale--interaction */proc logistic data=yahoo; model d(event='2')=gcat xcat gcat*xcat; run;proc logistic data=yahoo; class G_X (ref='00' param=reference); model d(event='2')=G_X; run;proc nlmixed data=yahoo; where gcat ne . and xcat ne .; if (gcat eq 0) and (xcat eq 0) then eta=a; if (gcat eq 0) and (xcat eq 1) then eta=a+b2; if (gcat eq 1) and (xcat eq 0) then eta=a+b1; if (gcat eq 1) and (xcat eq 1) then eta=a+b3; ll = (d=2)*eta - log(1+exp(eta)); model d ~ general(ll); parms a b1 b2 b3=0;run;

Constrained -2 log L = 2211.7 Unconstrained -2 log L = 2210.8

LRT is 0.9 on 1 d.f. p=0.34

Beta_2 is log OR (exposed non carriers)Beta_1 is log OR (carrier unexposed)Beta_3 is log OR (exposed carrier)

Power calculations: Quantohttp://hydra.usc.edu/gxe/

G, G-E, G-G, joint G G-E

Set MAF

Set Prev(E)

Set Penetrance Model

Set alpha, target power (N)