Putative cis-eQTL SNPs were tested for association with heroin addiction across both ancestry groups in the discovery cohort (UHS vs. population controls). Significantly associated SNPs were then tested for replication in the CIDR – Gelernter Study and the Australian Heroin Dependence Study. Observed SNP genotypes or imputed SNP genotype dosages were tested for association using logistic regression models, separately by cohort and by ancestry group, with adjustment for sex and principal component eigenvectors (see Supplement). SNP association results were compared using the Forest Plot Viewer (53) and combined via fixed-effects sample size-weighted meta-analyses, as used in prior multiancestry meta-analyses (54, 55). As shown in Figure 1, at each stage of the association testing, linkage disequilibrium among the tested SNPs was taken into account to compute the P value thresholds for declaring statistical significance (35, 36) (α=0.05 / number of independent tests): meta-analysis P<0.0050 based on 10 independent tests in the discovery stage and meta-analysis P<0.0125 based on 4 independent tests in the replication stage.
