Journal article
Whole-exome sequencing identifies genes associated with Tourette's disorder in multiplex families
Molecular psychiatry, Vol.26(11), pp.6937-6951
11/2021
DOI: 10.1038/s41380-021-01094-1
PMCID: PMC8501157
PMID: 33837273
Abstract
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.
Details
- Title: Subtitle
- Whole-exome sequencing identifies genes associated with Tourette's disorder in multiplex families
- Creators
- Xiaolong Cao - Rutgers, The State University of New JerseyYeting Zhang - Rutgers, The State University of New JerseyMohamed Abdulkadir - University Medical Center GroningenLi Deng - Rutgers, The State University of New JerseyThomas V Fernandez - Yale UniversityBlanca Garcia-Delgar - Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic Universitari, Barcelona, Spain.Julie Hagstrøm - Mental Health ServicesPieter J Hoekstra - University Medical Center GroningenRobert A King - Yale UniversityJustin Koesterich - Rutgers, The State University of New JerseySamuel Kuperman - University of IowaAstrid Morer - Centro de Investigacion en Red de Salud Mental (CIBERSAM), Instituto Carlos III, Madrid, Spain.Cara Nasello - Rutgers, The State University of New JerseyKerstin J Plessen - Mental Health ServicesJoshua K Thackray - Rutgers, The State University of New JerseyLisheng Zhou - Rutgers, The State University of New JerseyAndrea Dietrich - University Medical Center GroningenJay A Tischfield - Rutgers, The State University of New JerseyGary A Heiman - Rutgers, The State University of New JerseyJinchuan Xing - Rutgers, The State University of New JerseyTourette International Collaborative Genetics Study (TIC Genetics)
- Resource Type
- Journal article
- Publication Details
- Molecular psychiatry, Vol.26(11), pp.6937-6951
- DOI
- 10.1038/s41380-021-01094-1
- PMID
- 33837273
- PMCID
- PMC8501157
- NLM abbreviation
- Mol Psychiatry
- ISSN
- 1359-4184
- eISSN
- 1476-5578
- Grant note
- K08 MH099424 / NIMH NIH HHS R01 ES021462 / NIEHS NIH HHS R01 MH092293 / NIMH NIH HHS R01 MH115958 / NIMH NIH HHS R01 MH115963 / NIMH NIH HHS UL1 TR001863 / NCATS NIH HHS U24 MH068457 / NIMH NIH HHS
- Language
- English
- Date published
- 11/2021
- Academic Unit
- Psychiatry
- Record Identifier
- 9984293657202771
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