ASSOCIATION ANALYSIS OF THE DOPAMINE D-2 RECEPTOR GENE IN TOURETTES-SYNDROME USING THE HAPLOTYPE RELATIVE RISK METHOD

Comings et al. [1991: JAMA 266: 1793-1800] have recently reported a hi ghly significant association between Tourette's syndrome (TS) and a re striction fragment length polymorphism (RFLP) of the dopamine D-2 rece ptor gene (DRD2) locus. The Al allele of the DRD2 Taq I RFLP was prese nt in 45% of the Tourette patients compared with 25% of controls. We t ried to replicate this finding by using the haplotype relative risk (H RR) method for association analysis. This method overcomes a major pro blem of conventional case-control studies, where undetected ethnic dif ferences between patients and controls may result in a false-positive finding, by using parental alleles not inherited to the proband as con trol alleles. Sixty-one nuclear families encompassing an affected chil d and parents were typed for the DRD2 Taq I polymorphism. No significa nt differences in DRD2 Al allele frequency were observed between TS pr obands, subpopulations of probands classified according to tic severit y, or parental control alleles. Our data do not support the hypothesis that the DRD2 locus may act as a modifying gene in the expression of the disorder in TS probands. (C) 1994 Wiley-Liss, Inc.