Association and linkage studies of the TAQI A1 allele at the dopamine D2 receptor gene in samples of female and male alcoholics.

To address the controversy surrounding DRD2 and alcoholism, we performed linkage and association studies utilizing alcoholic men from high-density families largely uncontaminated by other psychopathology and female alcoholics for whom secondary drug dependence (averaging 10 years later onset) was a prominent feature. The males and females were combined for a total of 52 alcoholics, and compared to 30 controls screened for the absence of alcoholism and other psychopathology, revealing a significant association between the frequency of the TaqI A1 allele and alcoholism. However, linkage and family-based association studies conducted on 20 families of male alcoholics found no evidence for association or linkage between Taq A and alcoholism. The results of our population-based association study, placed in the context of the literature, suggest that minimizing psychopathology in control groups is probably a more important explanation for divergent results than either sampling error or population stratification. When combined with the complete lack of within-family evidence, we concluded that the association, while not appearing to be artifactual, is not specific to the alcoholism phenotype, per se.