@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 = "Funding Information: This research was also supported in part by an Informatics Starter Grant from the PhRMA Foundation (to Y. Bromberg). We thank all of the individuals involved in recruitment and assessment of the subjects reported in this study: Denmark: Nikoline Frost and Heidi B. Biernat (Copenhagen); Germany: Stephanie Enghardt, Yvonne Friedrich, Christiane Michel (Dresden), Jenny Schmalfeld (L{\"u}beck), Hanife Kling, and Ariane Saccarello (Ulm); Spain: Mar{\'i}a T. C{\'a}ceres, F{\'a}tima Carrillo, Marta Correa, Pilar G{\'o}mez-Garre, and Laura Vargas (Sevilla); the Netherlands: Vivian op de Beek (Amsterdam), Marieke Messchendorp (Groningen), Nicole Driessen, Nadine Schalk (Nijmegen), Noor Tromp (Alkmaar), Els van den Ban (Utrecht), Jolanda Blom, Rudi Bruggemans, and MariAnne Overdijk (Barendrecht); UK: Anup Kharod (London GOSH); USA: Sarah Jacobson (Cincinnati), Angie Cookman (Iowa City), Zoey Shaw (Mount Sinai/NKI), Julia Brillante, Daniela B. Colognori, Joseph Conerty, Alycia Davis, Joanne O'Brien, Carolyn Spiro, Donna Tischfield (Rutgers), Shannon Granillo, and JD Sandhu (Seattle Children's). Finally, we thank Adife Gulhan Ercan-Sencicek (Yale), Xin He (University of Chicago), Kathryn Roeder (CMU), Bernie Devlin (University of Pittsburgh), Helen Willsey (UCSF), the Willsey lab (UCSF), and all who may not have been mentioned. 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",
}