A Genetic Linkage Study of the D2 Dopamine Receptor Locus in Heavy Drinking and Alcoholism

Reports of an association between restriction fragment length polymorphisms (RFLPs) at the dopamine D2 receptor (DRD2) locus and alcoholism have suggested involvement of that locus in the aetiology of alcoholism. Sib pair linkage analyses were conducted in families multiply affected by alcoholism, using both the Taql 'A' RFLP and a microsatellite repeat polymorphism at the DRD2 locus. The 'Identical By Descent' analysis provided significant evidence of an effect of the DRD2 locus on the liability to develop heavy drinking (P < 0.0016) and Research Diagnostic Criteria alcoholism (P < 0.0003) in the first sample of families studied. However, this result was explicable by the segregation of alleles in a single large sibship, and it was not replicated in a second sample of families. The results do not support linkage between the DRD2 locus and alcoholism in most of the families studied. It remains possible that this locus influences the predisposition to alcoholism in some families.