Association analysis of the dopamine D₂receptor gene in Tourette's syndrome using the haplotype relative risk method

Abstract

Comings et al. [1991: JAMA 266: 1793-1800] have recently reported a highly significant association between Tourette's syndrome (TS) and a restriction fragment length polymorphism (RFLP) of the dopamine D2 receptor gene (DRD2) locus. The A1 allele of the DRD2 Taq I RFLP was present in 45% of the Tourette patients compared with 25% of controls. We tried to replicate this finding by using the haplotype relative risk (HRR) method for association analysis. This method overcomes a major problem of conventional case-control studies, where undetected ethnic differences between patients and controls may result in a false-positive finding, by using parental alleles not inherited to the proband as control alleles. Sixty-one nuclear families encompassing an affected child and parents were typed for the DRD2 Taq I polymorphism. No significant differences in DRD2 A1 allele frequency were observed between TS probands, subpopulations of probands classified according to tic severity, 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.

The ANKK1 Kinase Gene and Psychiatric Disorders

“…genotype has also been analyzed in a casecontrol genetic association study of Tourette's syndrome, which showed a significantly greater presence in patients (44.9 vs. 24.5%) (Comings et al 1991). Nevertheless, other reports have not replicated this finding (Nothen et al 1994;Gelernter et al 1994). …”

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

“…Thus, a model has been proposed in which frequent prefrontal activation during tic suppression may produce compensatory prefrontal cortex hypertrophy that aids in tic suppression [624,625], although it is not presently clear how such basal ganglia and prefrontal characteristics effects reward processing in TS. Variants in the DA receptor gene DRD 2 have also been associated with genetic risk for TS [626-628], but this finding is not consistent [629-633]. …”

The genetics of tourette syndrome

“…Furthermore, no association between the A1 allele and severity was observed [35]. Finally, using a family-based association strategy [48], did not find any evidence for a association between DRD2 and TS.…”