Genome-wide association study of Tourette&apos;s syndrome

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Genome-wide association study of Tourette's syndrome

Cited 130 time in Web of Science Cited 149 time in Scopus

Authors: Scharf, J. M.; Yu, D.; Mathews, C. A.; Neale, B. M.; Stewart, S. E.; Fagerness, J. A.; Evans, P.; Gamazon, E.; Edlund, C. K.; Service, S. K.; Tikhomirov, A.; Osiecki, L.; Illmann, C.; Pluzhnikov, A.; Konkashbaev, A.; Davis, L. K.; Han, B.; Crane, J.; Moorjani, P.; Crenshaw, A. T.; Parkin, M. A.; Reus, V. I.; Lowe, T. L.; Rangel-Lugo, M.; Chouinard, S.; Dion, Y.; Girard, S.; Cath, D. C.; Smit, J. H.; King, R. A.; Fernandez, T. V.; Leckman, J. F.; Kidd, K. K.; Kidd, J. R.; Pakstis, A. J.; State, M. W.; Herrera, L. D.; Romero, R.; Fournier, E.; Sandor, P.; Barr, C. L.; Phan, N.; Gross-Tsur, V.; Benarroch, F.; Pollak, Y.; Budman, C. L.; Bruun, R. D.; Erenberg, G.; Naarden, A. L.; Lee, P. C.; Weiss, N.; Kremeyer, B.; Berrio, G. B.; Campbell, D. D.; Cardona Silgado, J. C.; Ochoa, W. C.; Mesa Restrepo, S. C.; Muller, H.; Valencia Duarte, A. V.; Lyon, G. J.; Leppert, M.; Morgan, J.; Weiss, R.; Grados, M. A.; Anderson, K.; Davarya, S.; Singer, H.; Walkup, J.; Jankovic, J.; Tischfield, J. A.; Heiman, G. A.; Gilbert, D. L.; Hoekstra, P. J.; Robertson, M. M.; Kurlan, R.; Liu, C.; Gibbs, J. R.; Singleton, A.; Hardy, J.; Strengman, E.; Ophoff, R. A.; Wagner, M.; Moessner, R.; Mirel, D. B.; Posthuma, D.; Sabatti, C.; Eskin, E.; Conti, D. V.; Knowles, J. A.; Ruiz-Linares, A.; Rouleau, G. A.; Purcell, S.; Heutink, P.; Oostra, B. A.; McMahon, W. M.; Freimer, N. B.; Cox, N. J.; Pauls, D. L.

Abstract: Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P < 5 x 10(-8)); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P = 1.85 x 10(-6)). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal ( P = 3.6 x 10(-7) for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder.