ADH cluster was the only locus that was significantly associated with alcohol dependence at the genome-wide level in at least one individual sample. Most of the risk ADH variants were potentially functional. The most robust association was found at the ADH cluster. At least three GWASs detected significant association signals in Asians (34), Germans (33), European-Americans and African-Americans (36) at genome-wide level, and other four GWASs in Koreans (34), Germans (32) and European-Americans (22, 33, 35) and African-Americans (22) replicated them. There have also been numerous candidate gene studies that reported strong associations between ADH cluster and alcohol dependence (summarized by Luo et al. (43) 2006). Recent meta-analysis demonstrated that rs1229984 (Arg48His) at ADH1B (p=10−36) and rs698 (Ile350Val) at ADH1C (p=10−8) were highly strongly associated with alcohol dependence (6, 7), supporting the GWAS findings. ADHs are primary enzymes that are responsible for the oxidation of alcohol in the liver. Their activities have been well-known to influence the risk of becoming alcoholic.
