Whole-exome sequencing identifies genes associated with Tourette's disorder in multiplex families

Autor: Gary A. Heiman, Samuel Kuperman, Andrea Dietrich, Li Deng, Julie Hagstrøm, Yeting Zhang, Jinchuan Xing, Xiaolong Cao, Lisheng Zhou, Pieter J. Hoekstra, Cara Nasello, Astrid Morer, Jay A. Tischfield, Mohamed Abdulkadir, Blanca Garcia-Delgar, Joshua K. Thackray, Kerstin J. Plessen, Justin Koesterich, Thomas V. Fernandez, Robert A. King
Přispěvatelé: Clinical Cognitive Neuropsychiatry Research Program (CCNP), National Institute of Mental Health (US), Tourette Syndrome Association of New Jersey, National Institute of Environmental Health Sciences (US), Instituto de Salud Carlos III, Junta de Andalucía, Sociedad Andaluza de Neurología, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Jacques and Gloria Gossweiler Foundation, German Research Foundation, Tourette Association of America, National Institute for Health and Care Research (US), Tourette International Collaborative Genetics Study (TIC Genetics), Brown, L.W., Cao, X., Coffey, B.J., Gilbert, D.L., Hedderly, T., Heyman, I., Huyser, C., Kim, E., Kim, Y.S., Koh, Y.J., Leventhal, B.L., Madruga-Garrido, M., Maras, A., Mir, P., Münchau, A., Roessner, V., Song, D.H., State, M.W., Willsey, A.J., Zinner, S.H., Child Psychiatry, Paediatric Psychosocial Care, Amsterdam Neuroscience - Cellular & Molecular Mechanisms
Rok vydání: 2020
Předmět:
Zdroj: Molecular psychiatry
Molecular Psychiatry. Nature Publishing Group
Molecular psychiatry, vol. 26, no. 11, pp. 6937-6951
Digital.CSIC. Repositorio Institucional del CSIC
instname
Molecular psychiatry. Nature Publishing Group
ISSN: 1476-5578
1359-4184
Popis: Tourette’s Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein–protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.
This study was supported by a grant from the National Institute of Mental Health (R01MH092293 to GAH and JAT) and by a grant from the New Jersey Center for Tourette Syndrome (to GAH and JAT). This study was also supported by grants from the National Institute of Mental Health (K08MH099424 to TVF) and the National Institute for Environmental Health Science (R01 ES021462 for YSK and BLL). PM has received grants from the Instituto de Salud Carlos III (PI10/01674, PI13/01461), the Consejería de Economía, Innovación, Ciencia y Empresa de la Junta de Andalucía (CVI-02526, CTS-7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0741/2010, PI-0437-2012, PI-0471-2013), the Sociedad Andaluza de Neurología, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña, and the Jaques and Gloria Gossweiler Foundation. AM has received grants from the Fundacion Alicia Koplowitz and belongs to the research group of the Comissionat per Universitats i Recerca del Departmanent d’Innovacio (DIUE) 2009SGR1119. AM has received grants from the Deutsche Forschungsgemeinschaft (DFG: MU 1692/3-1, MU 1692/4-1, and FOR 2698). AJW received a Young Investigator Award from Tourette Association of America. IH declares that all research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre.
Databáze: OpenAIRE
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