Although twin and family-based studies show that about 50% of alcohol dependence (AD) risk is heritable, replicable findings have identified few corresponding genetic variants. Using a known variant, we used electronic health record data to develop and validate a phenotype for harmful alcohol exposure that could be used to identify unknown genetic variants in large samples. Linkage and candidate gene studies have consistently identified risk loci for the genes encoding the alcohol-metabolizing enzymes (Foroud et al., 2010). Similar findings have emerged from genome-wide association studies (GWAS) (Hart and Kranzler, 2015). A major limitation to gene finding for AD is the relatively small sample size of many of the published studies. The largest GWAS of AD to date included a discovery and replication sample of 16,087 subjects (Gelernter et al., 2014). That study confirmed previously identified risk loci mapped to the alcohol-metabolizing enzyme genes ADH1B in both European Americans (Arg48His or rs1229984, P = 1.17 × 10−31) and African Americans (AAs; Arg369Cys or rs2066702, P = 6.33 × 10−17) and ADH1C in AAs (Thr151Thr or rs2241894, P= 4.94 × 10−10). The
