Among the most biologically well-understood genetic variants associated with alcohol use disorders is the polymorphism rs1229984 in the enzyme alcohol dehydrogenase 1B (ADH1B). The minor A allele (in the coding strand) of rs1229984 causes an amino acid change at position 48 by replacing arginine with histidine, which increases the activity of the ADH1B enzyme that oxidizes ethanol to acetaldehyde (Edenberg and Foroud, 2013; Hurley and Edenberg, 2012). After consuming alcohol, elevated ADH1B activity has been hypothesized to transiently increase the level of acetaldehyde, leading to unpleasant effects that limit further drinking. Meta-analysis of this variant in Asian populations, where the rs1229984 A allele is common (allele frequency=0.7 in 1000 Genomes)(Abecasis et al., 2012), has demonstrated strong effects on the risk of developing alcohol-related disorders (OR 0.45: p=7×10−42) (Li et al., 2011). Recently, this polymorphism was shown to have a similar effect on risk of alcohol dependence in European and African Americans (African and European OR 0.34: p=6.6×10−10 (Bierut et al., 2012); European: p=1.17×10−31(Gelernter et al., 2014)), where the rs1229984 A allele is less common (European American frequency=0.05; African American frequency=0.02 in Exome Variant Server)(http://evs.gs.washington.edu/EVS/).
