The coding variants ADH1B*2, ADH1B*3, ADH1C*1 and ALDH2*2 all provide some protection against excessive alcohol consumption and thereby against alcohol dependence. The effect sizes for ADH1B*2 (rs1229984) and ALDH2*2 (rs671) are high for a complex disease. Presence of even a single ALDH2*2 allele leads to high levels of acetaldehyde in blood and a very strong flushing reaction. Although the ADH1B*2, ADH1B*3 and ADH1C*1 variants do not by themselves lead to high levels of acetaldehyde because an active ALDH2 enzyme so efficiently oxidizes it to acetate, they also provide significant protection. Allele frequencies of these coding SNPs differ widely among populations, as do the patterns of LD, and the impact of a variant can be modified by different environments, so it is important to broaden studies to a wider range of populations.
