ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry

A coding variant in ADH1B (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American case-control studies in which alcohol dependence was defined by DSM-IV criteria, and demonstrated a strong protective effect of the His48 variant (odds ratio of 0.34, 95% confidence interval 0.24, 0.48) for alcohol dependence, with genome-wide significance (6.6 × 10(−10)). The hypothesized mechanism of action involves an increased aversive reaction to alcohol; in keeping with this hypothesis, the same allele is strongly associated with a lower maximum number of drinks in a 24 hour period (lifetime), with p = 3×10(−13). We also tested the effects of this allele on the development of alcoholism in adolescents and young adults and demonstrated a significant protective effect. This variant has the strongest effect on risk for alcohol dependence of any tested in European populations.