ASSOCIATION AND LINKAGE STUDIES OF THE TAQI A1 ALLELE AT THE DOPAMINED-2 RECEPTOR GENE IN SAMPLES OF FEMALE AND MALE ALCOHOLICS

To address the controversy surrounding DRD2 and alcoholism, we perform ed linkage and association studies utilizing alcoholic men from high-d ensity families largely uncontaminated by other psychopathology and fe male alcoholics for whom secondary drug dependence (averaging 10 years later onset) was a prominent feature, The males and females were comb ined for a total of 52 alcoholics, and compared to 30 controls screene d for the absence of alcoholism and other psychopathology, revealing a significant association between the frequency of the TaqI A1 allele a nd alcoholism, However, linkage and family-based association studies c onducted on 20 families of male alcoholics found no evidence for assoc iation or linkage between Tag A and alcoholism. The results of our pop ulation-based association study, placed in the context of the literatu re, suggest that minimizing psychopathology in control groups is proba bly a more important explanation for divergent results than either sam pling error or population stratification, When combined with the compl ete lack of within-family evidence, we conclude that the association, while not appearing to be artifactual, is not specific to the alcoholi sm phenotype, per se. (C) 1995 Wiley-Liss, Inc.