Our results support ZNF804A as one of the few susceptibility genes for heroin addiction with replicable associations and provide further evidence that this gene has pleiotropic effects on multiple psychiatric diseases. We found that the two-SNP haplotype association with heroin addiction remained after excluding cases with comorbid cocaine abuse, albeit to a lesser extent with the reduced sample size. Given that heroin and cocaine abuse were highly comorbid in the UHS, follow-up in other cohorts will be needed to assess the pleiotropic or independent associations of ZNF804A SNPs with addiction to heroin and other drugs. Taken together with prior work showing that these disease-associated SNPs influence ZNF804A gene regulation in human brain, the ZNF804A gene region merits future study to establish the underlying mechanism that confers risk on heroin addiction.
