A GENETIC-LINKAGE STUDY OF THE D-2 DOPAMINE-RECEPTOR LOCUS IN HEAVY DRINKING AND ALCOHOLISM

Background. Reports of an association between restriction fragment len gth polymorphisms (RFLPs) at the dopamine D-2 receptor (DRD2) locus an d alcoholism have suggested involvement of that locus in the aetiology of alcoholism. Method. Sib pair linkage analyses were conducted in fa milies multiply affected by alcoholism, using both the Taql 'A' RFLP a nd a microsatellite repeat polymorphism at the DRD2 locus. Results. Th e '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 n ot replicated in a second sample of families. Conclusions. The results do not support linkage between the DRD2 locus and alcoholism in most of the families studied. It remains possible that this locus influence s the predisposition to alcoholism in some families.