This article reviewed family, adoption, and twin studies of AUD. The heritability of AUD has been reported to range from 50 to 70% based on twin studies. This study briefly reviews studies of gene-environment interaction in AUD and also provides evidence of gene-environment interaction using aldehyde dehydrogenase-2 (ALDH2) genotype frequencies in AUD patients. Mitochondrial ALDH2 plays a central role in human acetaldehyde metabolism. The variant allele ALDH2^*2 commonly occurs in approximately 40% of East Asians including Japanese. ALDH2^*2 homozygotes exhibit essentially no ALDH2 activity, while heterozygotes exhibit only a markedly reduced activity. East Asians deficient in ALDH2 exhibit a very high accumulation of acetaldehyde in circulating blood following alcohol ingestion, resulting in facial flushing, tachycardia, headache, nausea, and other physically uncomfortable reactions. Consequently, the association of ALDH2^*2 and reductions in alcohol consumption among Asians has been consistently documented. Genetic epidemiologic studies indicate that the presence of homozygous ALDH2^*2 significantly protects against the development of AUD, but the heterozygous allele only partially protects against AUD. The frequency of the ALDH2^*2 allele among Japanese patients with AUD provides a unique opportunity to examine this particular gene in a gene-environment interaction related to AUD. The change in the ALDH2 genotype distributions among Japanese patients with AUD from 1979 to 2010 showed a continuous increase from 2.5% in 1979, to 8.0% in 1986, 13.0% in 1992, 14.0% in 2001-2005, and 15.4% in 2006-2010. These findings suggest that the environmental influences on subjects with inactive ALDH2 have continued to gradually strengthen in Japanese society, leading to a continuing increase in the prevalence of persons with AUD carrying the inactive ALDH2 genotype.
 Finally, we showed preliminary results of a treatment outcome study of AUD in Kurihama Medical and Addiction Center. Our outcome study showed that the abstinence rate was higher in AUD patients with depression treated with acamprosate than in those without depression treated similarly, and these results suggest that acamprosate is particularly effective for AUD patients with depression. However, since these results are preliminary, they should be interpreted with caution.
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