Journal article
De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis
Cell reports (Cambridge), Vol.24(13), pp.3441-3454
09/25/2018
DOI: 10.1016/j.celrep.2018.08.082
PMCID: PMC6475626
PMID: 30257206
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.
Details
- Title: Subtitle
- De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis
- Creators
- Sheng Wang - University of California, San FranciscoJeffrey D. Mandell - University of California, San FranciscoYogesh Kumar - Purdue University West LafayetteNawei Sun - University of California, San FranciscoMontana T. Morris - University of California, San FranciscoJuan Arbelaez - University of California, San FranciscoCara Nasello - Rutgers, The State University of New JerseyShan Dong - University of California, San FranciscoClif Duhn - University of California, San FranciscoXin Zhao - University of Iowa, Microbiology and ImmunologyZhiyu Yang - Purdue University West LafayetteShanmukha S. Padmanabhuni - Purdue University West LafayetteDongmei Yu - Massachusetts General HospitalRobert A. King - Yale UniversityAndrea Dietrich - University Medical Center GroningenNajah Khalifa - Uppsala UniversityNiklas Dahl - Science for Life LaboratoryAlden Y. Huang - University of California, Los AngelesBenjamin M. Neale - Broad InstituteCarol A. Mathews - Broad InstituteGiovanni Coppola - University of California, Los AngelesJeremiah M. Scharf - Karolinska InstitutetTourette International Collaborative Genetics Study (TIC Genetics)Tourette Syndrome Genetics Southern and Eastern Europe Initiative (TSGENESEE)Tourette Association of America International Consortium for Genetics (TAAICG)Thomas V. Fernandez - Yale UniversityJoseph D. Buxbaum - Icahn School of Medicine at Mount SinaiSilvia De Rubeis - Icahn School of Medicine at Mount SinaiDorothy E. Grice - Icahn School of Medicine at Mount SinaiJinchuan Xing - Rutgers, The State University of New JerseyGary A. Heiman - Rutgers, The State University of New JerseyJay A. Tischfield - Rutgers, The State University of New JerseyPeristera Paschou - Purdue University West LafayetteA. Jeremy Willsey - University of California, San FranciscoMatthew W State - University of California, San Francisco
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.24(13), pp.3441-3454
- DOI
- 10.1016/j.celrep.2018.08.082
- PMID
- 30257206
- PMCID
- PMC6475626
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Grant note
- name: NIMH Repository and Genomics Resource, award: U24MH068457; DOI: 10.13039/100000025, name: National Institute of Mental Health, award: R01MH092290, R01MH092291, R01MH092292, R01MH092293, R01MH092513, R01MH092516, R01MH092520, R01MH092289, K08MH099424; name: Human Genetics Institute of New Jersey; name: New Jersey Center for Tourette Syndrome and Associated Disorders; name: Weill Institute for Neurosciences; name: Overlook International Foundation; DOI: 10.13039/100000002, name: NIH, award: M#UM1HG006504-05; DOI: 10.13039/100000051, name: National Human Genome Research Institute; DOI: 10.13039/100000050, name: National Heart, Lung, and Blood Institute; name: GSP Coordinating Center, award: U24, HG008956; DOI: 10.13039/501100004587, name: Instituto de Salud Carlos III, award: PI10/01674, PI13/01461; name: Consejería de Economía, Innovación, Ciencia y Empresa de la Junta de Andalucía, award: CVI-02526, CTS-7685; name: Consejería de Salud y Bienestar Social de la Junta de Andalucía, award: PI-0741/2010, PI-0437-2012, PI-0471-2013; DOI: 10.13039/501100008997, name: Sociedad Andaluza de Neurología; DOI: 10.13039/100008062, name: Fundación Alicia Koplowitz; DOI: 10.13039/100008061, name: Fundación Mutua Madrileña; name: Jaques and Gloria Gossweiler Foundation; DOI: 10.13039/100008062, name: Alicia Koplowitz Foundation; DOI: 10.13039/501100001659, name: Deutsche Forschungsgemeinschaft, award: MU 1692/3-1, MU 1692/4-1, SFB 936; DOI: 10.13039/501100004359, name: Swedish Research Council, award: 2015-02424; DOI: 10.13039/100001797, name: PhRMA Foundation; name: Mindich Child Health and Developmental Institute at the Icahn School of Medicine at Mount Sinai; name: Seaver Foundation; name: Stanley Center for Psychiatric Research; name: NIHR Great Ormond Street Hospital Biomedical Research Centre
- Language
- English
- Date published
- 09/25/2018
- Academic Unit
- Psychiatry
- Record Identifier
- 9984293756302771
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