The four SNPs significantly associated with heroin addiction in the discovery cohort were then tested in African Americans from the CIDR – Gelernter Study and Australians of European ancestry from the Australian Heroin Dependence Study (Figure 1). Results are presented in Table S7. The rs3778150 association with heroin addiction was significantly replicated at P=6.8×10−5, well below the corrected replication threshold P<0.0125, based on an overall α=0.05 corrected for 4 independent tests (35, 36). Meta-analysis of rs3778150 combining discovery and replication cohorts resulted in P=4.3×10−8. As shown by the OR estimates in Figure 2, the rs3778150 minor allele (C) was consistently associated with an increased heroin addiction risk in participants of European ancestry (1.28 in the UHS and 1.23 in the Australian Heroin Dependence Study) and African Americans (1.15 in the UHS and 1.20 in the CIDR – Gelernter Study), and it was associated at P<0.05 in both UHS ancestry groups and the Australian Heroin Dependence Study. The direction of the rs3778150-C association was consistent in the CIDR – Gelernter Study but with P=0.17; this cohort was smaller than the others
