Our study identified the KAT2B SNP rs9829896 as having a novel and statistically significant association with drug abuse among AAs. We replicated the rs9829896 association in an independent cohort of AAs and found that its C allele was associated with reduced risk of drug abuse, showing consistent ORs (0.68 and 0.53) across the AA cohorts. This protective effect was shared across multiple drug categories, rather than being driven by any specific drug. We implicated rs9829896 as a cis-eQTL for the KAT2B gene and as a trans-eQTL for the CREBBP and OPRM1 genes, using mRNA expression levels measured in human prefrontal cortex. The proteins encoded by CREBBP and OPRM1 are members of the cAMP and dopamine pathways, respectively, and both pathways have been widely studied for their roles in drug addiction. Our regulatory evidence suggests that rs9829896 may be a biologically important SNP that may contribute to differential expression of cAMP and dopamine pathway genes in human prefrontal cortex among AAs: pathways by which the C allele may have its observed protective effect on risk of drug abuse also among AAs.
