@article{6a0956441667431597b7d2b9b5cd9d73,
title = "De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis",
abstract = "We previously established the contribution of de novo damaging sequence variants to Tourette disorder (TD) through whole-exome sequencing of 511 trios. Here, we sequence an additional 291 TD trios and analyze the combined set of 802 trios. We observe an overrepresentation of de novo damaging variants in simplex, but not multiplex, families; we identify a high-confidence TD risk gene, CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3); we find that the genes mutated in TD patients are enriched for those related to cell polarity, suggesting a common pathway underlying pathobiology; and we confirm a statistically significant excess of de novo copy number variants in TD. Finally, we identify significant overlap of de novo sequence variants between TD and obsessive-compulsive disorder and de novo copy number variants between TD and autism spectrum disorder, consistent with shared genetic risk. Wang et al. expand their earlier exome-sequencing work in TD, adding 291 trios and conducting combined analyses suggesting de novo variants carry more risk in individuals with unaffected parents, establishing de novo structural variants as risk factors, identifying CELSR3 as a risk gene, and implicating cell polarity in pathogenesis.",
author = "{Tourette International Collaborative Genetics Study (TIC Genetics), Tourette Syndrome Genetics Southern and Eastern Europe Initiative (TSGENESEE), Tourette Association of America International Consortium for Genetics (TAAICG)} and Sheng Wang and Mandell, {Jeffrey D.} and Yogesh Kumar and Nawei Sun and Morris, {Montana T.} and Juan Arbelaez and Cara Nasello and Shan Dong and Clif Duhn and Xin Zhao and Zhiyu Yang and Padmanabhuni, {Shanmukha S.} and Dongmei Yu and King, {Robert A.} and Andrea Dietrich and Najah Khalifa and Niklas Dahl and Huang, {Alden Y.} and Neale, {Benjamin M.} and Giovanni Coppola and Mathews, {Carol A.} and Scharf, {Jeremiah M.} and Fernandez, {Thomas V.} and Buxbaum, {Joseph D.} and {De Rubeis}, Silvia and Grice, {Dorothy E.} and Jinchuan Xing and Heiman, {Gary A.} and Tischfield, {Jay A.} and Peristera Paschou and {Jeremy Willsey}, A. and State, {Matthew W.} and Mohamed Abdulkadir and Benjamin Bodmer and Yana Bromberg and Brown, {Lawrence W.} and Cheon, {Keun Ah} and Coffey, {Barbara J.} and Li Deng and Lonneke Elzerman and Carolin Fremer and Blanca Garcia-Delgar and Gilbert, {Donald L.} and Julie Hagstr{\o}m and Tammy Hedderly and Isobel Heyman and Hoekstra, {Pieter J.} and Hong, {Hyun Ju} and Chaim Huyser and Cheston Berlin",
note = "Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = sep,
day = "25",
doi = "10.1016/j.celrep.2018.08.082",
language = "English (US)",
volume = "24",
pages = "3441--3454.e12",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "13",
}