The genetic transmission of alcoholism: implications for prevention

Evidence obtained from adoption and twin studies suggests an important hereditary component in alcoholism. Following our initial observation that the A1 allele of the D2 dopamine receptor (DRD2) gene was associated with alcoholism, a number of studies, both in the United States and abroad, have attempted to replicate and extend this finding in different Caucasian populations. In eight independent studies containing a total of 444 heterogeneous alcoholics (less severe and severe) and 495 heterogeneous controls (alcoholics excluded or not excluded), the prevalence of the A1 allele was 45.5% in the former group compared to 25.7% in the latter group (p < 10-7). In 176 severe alcoholics and 176 controls free of alcoholism, the prevalence of the A1 allele was 49.4% in the former group compared to 17.0% in the latter group (p < 10-8). The severity of alcoholism and the types of controls used are key determinants in A1 allelic association with alcoholism. The total evidence at hand suggests that the DRD2 A1 allele may represent the most prominent single gene determinant of susceptibility to severe alcoholism. However, the larger role is still played by environmental factors and other genes.