ADH1B and ALDH2 play a central role in the metabolism of alcohol in humans, and the functional impact of their two missense polymorphisms rs1229984 and rs671 has been extensively reviewed elsewhere.24, 25 In vivo, individuals who carry at least one copy of rs1229984 eliminate ethanol more quickly after heavy drinking and have lower blood alcohol concentrations in comparison to homozygous wild-type individuals.55, 56 Thus, individuals who carry at least one copy of rs1229984 are less exposed to circulating ethanol and might be less likely to develop a tolerance and dependence to alcohol, as previously speculated.55, 56 Our findings provide additional strong evidence of ADH1B rs1229984 as the variant in the ADH gene cluster with the largest impact on alcohol consumption, as previously reported.57, 58 On the other hand, rs671 impairs the processing of ALDH2, causing an accumulation in the body of acetaldehyde, which is toxic and leads to undesirable reactions, including nausea.56, 59 Early work demonstrated the strong effect of a single non-functional allele at this locus, as heterozygotes and homozygotes for rs671 (GA and AA genotypes) are deficient in
