ADH1B and ALDH2 are the genes most strongly associated with risk for alcoholism. Coding variants in both of these genes are strongly protective. They probably decrease alcoholism risk by increasing local acetaldehyde levels, either because ethanol is oxidized more rapidly or because acetaldehyde is oxidized more slowly. The exact balance between the rates of ethanol and acetaldehyde oxidation could be crucial in determining acetaldehyde concentrations within cells, such that small differences in the relative activities of ADH and ALDH might produce significant differences in acetaldehyde concentration (Kitson 1999). Because of this delicate balance, the effects of variations in ADH and ALDH genes on risk for alcoholism can be demonstrated independently—that is, researchers can determine differences in risk between people carrying different alleles of one gene but identical alleles of the other genes (e.g., Chen et al. 1999b; Thomasson et al. 1991).
