Beta Polypeptide), ADH1C (Alcohol Dehydrogenase 1C (class I), Gamma Polypeptide), ALDH2 (Aldehyde Dehydrogenase 2 Family Member, only in some Asian samples), SLC39A8 (Solute Carrier Family 39 Member 8), GCKR (Glucokinase Regulator), and CRHR1 (Corticotropin Releasing Hormone Receptor 1). In the context of the known extensive polygenicity underlying AUD and AUDIT-P, we anticipate that additional significant risk loci can be identified by increasing sample size; this is the pattern for GWAS of heterogenous complex traits in general also. We characterize both AUD itself and AUDIT-P, as “problematic alcohol use” (PAU). To identify additional risk variants and enhance our understanding of the genetic architecture of PAU, we conducted genome-wide meta-analysis of AUD and AUDIT-P in 435,563 individuals of European ancestry. Our understanding of the genetic architecture of PAU in African populations lags far behind that in Europeans; the largest sample of African ancestry individuals published so far is 56,648 in the Million Veteran Program (MVP) [3] and results have not moved beyond a single genomic region that includes ADH1B. We limited the focus here to European samples because we could not achieve a substantial increment in African-ancestry subjects over previous studies.
