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Chunk #15 — Discussion

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Replication of ZNF804A gene variant associations with risk of heroin addiction.
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Our study independently replicated the associations of the ZNF804A SNPs rs7597593 and rs1344706 and their haplotype with heroin addiction. Such replicable genetic associations with heroin addiction are limited. This replication may also be viewed as a generalization, as our results showed that the associations initially reported in Han Chinese extend to other ancestries, particularly European ancestry. Sun et al. (in press) first identified these heroin addiction associations in a Han Chinese dataset (N=1,035 DSM-IV defined cases and 2,887 community-based controls). Consistent with the prior report, both the rs7597593-T and rs1344706-A alleles and their corresponding haplotype were associated with increased risk of heroin addiction in our European American dataset. No statistically significant SNP or haplotype associations were observed in our African American dataset, but rs1344706-A and its risk haplotype with rs7597593-T presented consistent directions across the ancestry groups and remained associated at P<0.05 in our multiancestry meta-analyses. Similar magnitudes of rs1344706-A association have now been observed across diverse ancestries: odds ratios of 1.16 in Han Chinese (Sun et al., in press) and 1.13 in our meta-analysis of European Americans and African Americans.