@article{ddea5d97cdf84e44a040d7881637cc1f,
title = "De Novo Coding Variants Are Strongly Associated with Tourette Disorder",
abstract = "Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 trios from the Tourette Syndrome Association International Consortium on Genetics (511 total). We observe strong and consistent evidence for the contribution of de novo likely gene-disrupting (LGD) variants (rate ratio [RR] 2.32, p = 0.002). Additionally, de novo damaging variants (LGD and probably damaging missense) are overrepresented in probands (RR 1.37, p = 0.003). We identify four likely risk genes with multiple de novo damaging variants in unrelated probands: WWC1 (WW and C2 domain containing 1), CELSR3 (Cadherin EGF LAG seven-pass G-type receptor 3), NIPBL (Nipped-B-like), and FN1 (fibronectin 1). Overall, we estimate that de novo damaging variants in approximately 400 genes contribute risk in 12% of clinical cases.",
keywords = "TIC Genetics, TSAICG, Tourette disorder, Tourette syndrome, de novo variants, gene discovery, whole-exome sequencing",
author = "{Tourette International Collaborative Genetics (TIC Genetics)} and {Tourette Syndrome Association International Consortium for Genetics (TSAICG)} and {Tourette Syndrome Association International Consortium for Genetics (TSAICG)} and Willsey, {A. Jeremy} and Fernandez, {Thomas V.} and Dongmei Yu and King, {Robert A.} and Andrea Dietrich and Jinchuan Xing and Sanders, {Stephan J.} and Mandell, {Jeffrey D.} and Huang, {Alden Y.} and Petra Richer and Louw Smith and Shan Dong and Samocha, {Kaitlin E.} and Mohamed Abdulkadir and Julia Bohnenpoll and Yana Bromberg and Brown, {Lawrence W.} and Cheon, {Keun Ah} and Coffey, {Barbara J.} and Li Deng and Lonneke Elzerman and Odette Fr{\"u}ndt and Blanca Garcia-Delgar and Erika Gedvilaite and Gilbert, {Donald L.} and Grice, {Dorothy E.} and Julie Hagstr{\o}m and Tammy Hedderly and Heiman, {Gary A.} and Isobel Heyman and Hoekstra, {Pieter J.} and Hong, {Hyun Ju} and Chaim Huyser and Laura Ibanez-Gomez and Kim, {Young Key} and Kim, {Young Shin} and Koh, {Yun Joo} and Sodahm Kook and Samuel Kuperman and Andreas Lamerz and Bennett Leventhal and Ludolph, {Andrea G.} and {L{\"u}hr da Silva}, Claudia and Marcos Madruga-Garrido and Athanasios Maras and Pablo Mir and Astrid Morer and Alexander M{\"u}nchau and Grados, {Marco A.} and Singer, {Harvey S.}",
note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = may,
day = "3",
doi = "10.1016/j.neuron.2017.04.024",
language = "English (US)",
volume = "94",
pages = "486--499.e9",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "3",
}