Gene-based association analysis identified 66 genes that were associated with PAU at GWS (p < 2.64 × 10−6, Supplementary Table 4). DRD2, which has been extensively studied in many fields of neuroscience, was among these genes and was previously reported in both UKB [4] and MVP phase1 [3]. Among the 66 genes, 46 are novel, including ADH4 (Alcohol Dehydrogenase 4 (class II), Pi polypeptide), ADH5 (Alcohol Dehydrogenase 5 (class III), Chi Polypeptide), and ADH7 (Alcohol Dehydrogenase 7 (class IV), Mu or Sigma Polypeptide), extending alcohol metabolizing gene associations beyond the well-known ADH1B and ADH1C; SYNGAP1 (Synaptic Ras GTPase Activating Protein 1), BDNF (Brain-Derived Neurotrophic Factor), and others. Certain genes show associations with multiple traits including previous associations with AUDIT-C (4 genes in MVP phase1, 12 genes in UKB), total AUDIT score (19 genes in UKB), and DrnkWk (46 genes in GSCAN, which includes results for DrnkWk after MTAG (multi-trait analysis of GWAS) [10] analysis).
