Because ALDH2 specifically affects alcohol use via a known mechanism of altered alcohol metabolism, it is not likely to contribute to the same largely genetic latent factor that accounts for a large proportion of the variance in both alcohol use and other externalizing behaviors (Krueger et al., 2002). Therefore, environmental moderators of genetic influences upon alcohol use shown in twin and other family-based designs, as well as in candidate gene studies involving polymorphisms in genes active within the nervous system, may not similarly moderate the effects of ALDH2 polymorphism. However, indirect evidence indicates that the strength of the effect of ALDH2 upon drinking may be influenced by the environment. Higuchi et al. (1994) noted that between 1979 and 1992, a progressively greater proportion of alcoholics in Japan possessed the ALDH2*2 allele. This change is presumed to be the result of sociocultural shifts in Japan during the interim years, resulting in increased prevalence of alcohol use (Higuchi, 2007). These results imply, albeit indirectly, that the protection against maladaptive alcohol use afforded by possession of the ALDH2*2 allele may be attenuated by environments where drinking is more common, or social pressures to drink are high.
