The ALDH2–2 allele occurs commonly in people of Asian ancestry but is not seen in most other racial groups. Higuchi and colleagues (1994) compared the frequencies of the ALDH2–1 and ALDH2–2 alleles in groups of Japanese alcoholics at different time periods. This analysis found that the protective effect of the heterozygous genotype was decreasing over time in Japanese males (i.e., the number of alcoholics who were heterozygous increased over time). The authors suggested that this pattern could be most plausibly interpreted as a GxE interaction effect, in which the increasing social pressures on Japanese males to drink with colleagues after work reduced the protective effect of the heterozygous genotype. Examples of such GxE interaction effects in the alcoholism literature are rare, however.
