Genome scan for Tourette disorder in affected-sibling-pair and multigenerational families

Abstract

Tourette disorder (TD) is a neuropsychiatric disorder with a complex mode of inheritance and is characterized by multiple waxing and waning motor and phonic tics. This article reports the results of the largest genetic linkage study yet undertaken for TD. The sample analyzed includes 238 nuclear families yielding 304 "independent" sibling pairs and 18 separate multigenerational families, for a total of 2,040 individuals. A whole-genome screen with the use of 390 microsatellite markers was completed. Analyses were completed using two diagnostic classifications: (1) only individuals with TD were included as affected and (2) individuals with either TD or chronic-tic (CT) disorder were included as affected. Strong evidence of linkage was observed for a region on chromosome 2p (-log P = 4.42, P = 3.8 x 10(-5) in the analyses that included individuals with TD or CT disorder as affected. Results in several other regions also provide moderate evidence (-log P >2.0) of additional susceptibility loci for TD.

Figure  1.

Z_pairs scores for ASP families, with use of TD (broken line) and TD + CT (solid line) as diagnostic groupings (MERLIN)

Figure  2.

Z_pairs −logP scores for the multigenerational pedigrees, with use of TD (broken line) and TD + CT (solid line) as diagnostic groupings (SIMWALK2).

Figure  3.

Z_pairs −logP scores for the combined sample of ASP and multigenerational families, with use of TD (broken line) and TD + CT (solid line) as diagnostic groupings (MERLIN and SIMWALK2).

Figure  4.

Z_pairs −logP scores for fine mapping of chromosome 2p, with use of TD and TD + CT as diagnostic groupings (MERLIN and SIMWALK2). The dotted line represents TD-only genome-scan markers; the dotted and broken line represents TD-only fine-mapping markers; the broken line represents TD + CT genome-scan markers; and the solid line represents TD + CT fine-mapping markers.