The majority of association studies investigating the role of alcohol-metabolizing genes in risk for alcohol-use disorders have focused on the well-characterized coding variants within ADH1B, ADH1C, and ALDH2 and on the phenotype of alcohol dependence. There are three different ADH1B alleles (33). The reference allele is ADH1B*1, which encodes the β1 subunit with an arginine at amino-acid positions 48 (Arg48) and 370 (Arg370). ADH1B*2, a common allele in Asians, encodes the β2 subunit with a histidine at position 48 (His48). The ADH1B*3 allele, which encodes the β3 subunit with a cysteine at position 370 (Cys370), is found primarily in people of African descent. Amino-acid substitutions at positions 48 (ADH1B*2) and 370 (ADH1B*3) result in 70–80-fold higher enzyme activity compared with that produced by the ADH1B*1 allele (33). The rapid conversion of ethanol to acetaldehyde causes facial flushing and aversive effects after alcohol consumption and is protective against alcohol dependence (103) (Figure 2). A meta-analysis of the ADH1B*2 allele in Han Chinese and Japanese showed that individuals who are homozygous for this variant (His48/His48) have a fivefold decrease in risk for
