Meta-analyses were conducted to determine the magnitude of relationships between polymorphisms in 2 genes, ALDH2 and ADH1B, with alcohol dependence in Asians. For each gene, possession of 1 variant [asterisk]2 allele was protective against alcohol dependence, and possession of a 2nd [asterisk]2 allele did not offer significant additional protection. The protective effects of these 2 gene polymorphisms were independent. Diagnostic criteria, recruitment strategy, and Japanese ethnicity moderated the effect of ALDH2[asterisk]2. Recruitment strategy and gender moderated the effect of ADH1B[asterisk]2. These findings highlight the importance of methodological issues and potential gene-gene and gene-environment interactions that must be considered when examining relationships between genetic polymorphisms and phenotypes.