The KAT2B gene region has not been previously implicated for any substance abuse-related phenotypes, but SNPs in this region were nominally significant in two GWAS of psychiatric traits: (1) schizophrenia and bipolar disorder using GAIN EAs(Wang et al., 2010) and (2) temperament in bipolar disorder using EAs from the Bipolar Genome Study (BiGS).(Greenwood et al., 2012) None of the seven SNPs implicated in the GAIN GWAS were associated with drug abuse in our study (Table S15). However, all four of the SNPs implicated in the BiGS GWAS were associated at P<0.05 in our multiancestry GWAS meta-analysis of drug abuse (lowest P=1.20×10−4, Table S15), and their associations had smaller P values and stronger magnitudes of association in AAs compared to EAs. Linkage disequilibrium patterns between rs9829896 and each of the 11 previously implicated SNPs (Figures S5 and S6) show high D’ values (up to 1 in both EUR and AFR) but low to modest r2 values (r2≤0.41 in EUR and r2≤0.25 in AFR). These prior implications give credence to KAT2B as a genetic risk factor for drug abuse behavior and mental disorders more broadly, but suggest that different alleles across KAT2B may give rise to disorder-specific associations.
