ASSOCIATION ANALYSIS IN AN EVOLUTIONARY CONTEXT - CLADISTIC-ANALYSIS OF THE DRD2 LOCUS TO TEST FOR ASSOCIATION WITH ALCOHOLISM

Previous studies testing the dopamine D2 receptor (DRD2) locus for ass ociation with alcoholism have produced conflicting results. Failure to screen controls for substance abuse and failure to assess alcoholics for severity have been proposed as causes for the inability of some st udies to detect an association. We have reevaluated the involvement of DRD2 mutations in susceptibility to alcoholism with a cladistics-base d association analysis after restricting an alcoholic sample to more s evere cases. For the present study we tested 55 alcoholic probands and 80 normal controls for differences in the frequency of six haplotypes at the DRD2 locus. The haplotypes were derived from five di-allelic p olymorphisms spanning all but the first exon of the DRD2 gene. A clado gram constructed from the haplotypes provided the evolutionary context for a nested statistical analysis. We found no significant evidence f or association of the DRD2 haplotypes analyzed with the more severe al coholic phenotype. (C) 1998 Wiley-Liss, Inc.