Rs1799971 was not significantly associated with heroin addiction in any of the cohorts or ancestry groups individually or in a meta-analysis (P=0.12), although its direction of association generally suggested that the major allele (A) conferred an increased risk with heroin addiction (Figure S7). Given the indication of a shared haplotype background between rs3778150 and rs1799971 in the EUR panel, we constructed the two-SNP haplotypes and tested their associations with heroin addiction across all case-control cohorts and ancestry groups. As shown in Table 2, the haplotype carrying both the rs3778150-C and rs1799971-A alleles was consistently and significantly associated with increased risk of heroin addiction for each cohort and for both European Americans and African Americans: meta-analysis P=1.5×10−6. The haplotype carrying rs1799971-A without rs3778150-C was not associated with heroin addiction in any of the cohorts or ancestry groups: meta-analysis P=0.79.
