In summary, the rs9829896-C allele was associated with reduced risk of drug abuse, reduced KAT2B and CREBBP expression, and increased OPRM1 expression, all specifically in AAs. Several lines of evidence suggest that the newly implicated KAT2B gene and its rs9829896 SNP have biological plausibility for influencing abuse of drugs, including prior implication for psychiatric traits and direct connections to members of the cAMP and dopamine pathways (CREBBP and OPRM1, respectively) that play important roles in drug addiction. Our study also provided support to prior GWAS findings for marijuana use disorder,(Agrawal et al., 2014) showing that the missense SNP rs9891146-T allele in the C17orf58 gene was associated with increased risk of drug abuse in general, corroborating its association primarily in EAs, and adding novel regulatory evidence that this SNP correlates with C17orf58 expression. Altogether, our findings highlight KAT2B and C17orf58 as genetic susceptibility factors for drug abuse and demonstrate the importance of considering their effects across ancestry groups.
