Findings of association studies depend on inclusion criteria and quality of the case and control subjects. Approximately 10% of Japanese alcoholics (Higuchi et al. 1994) develop their disease despite having the inactive (protective) ALDH2 encoded by either heterozygous lys-glu or homozygous lys-lys. Compared with the entire alcoholic population, the heterogeneity of alcoholism is considered to be relatively low in this genetically defined subgroup. Such alcoholics are considered to be advantageous for the identification of variations that produce minor effects; otherwise, the potential association may be masked by genetic variants with high effect.
