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Tourette syndrome (TS) has a significant genetic component, yet no TS susceptibility genes have been identified definitively. Several studies have determined that first-degree relatives of patients with TS have at least a 5- to 15-fold increased risk of developing the disorder compared with the general population, an increase that represents one of the highest familial recurrence risks among neuropsychiatric diseases that are inherited in a non-Mendelian fashion.1 Recently, Slit- and Trk-like 1 (SLITRK1) was proposed as a candidate TS susceptibility gene, and a noncoding polymorphism in the 3′ untranslated region of this gene (var321) was reported to be associated with TS in a case–control sample.2 Additional studies in small samples or population isolates have failed to replicate this association.3,4 As part of a 20-year collaborative effort, the Tourette Syndrome Association International Consortium for Genetics (TSAICG) has systematically collected a clinical sample of over 1,000 patients with TS and their family members.5 We chose to screen these individuals for SLITRK1 var321 to determine a more accurate estimate of the prevalence of this variant in the white TS clinic population and to test for any association between var321 and TS.
Methods.
A total of 2,300 individuals from 646 independently ascertained nuclear families were recruited from tic disorder specialty clinics from the United States, Canada, Great Britain, and The Netherlands. A total of 1,048 individuals (172 parents and 876 offspring) were diagnosed with either TS (989 subjects) or chronic tics (CT) (59 subjects) (e-Methods on the Neurology® Web site at www.neurology.org). A total of 440 …
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