Genome-wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
- Department of Child and Adolescent Psychiatry and Psychotherapy
- Democritus University of Thrace
- Purdue University
- Harvard University
- Broad Institute of Harvard University and MIT
- University of Copenhagen
- University of Catania
- Sorbonne Université
- University of Duisburg-Essen
- Hannover Medical School (MHH)
- Utrecht University
- Ulm University
- Vrije Universiteit Amsterdam (VU)
- Medical University of Warsaw
- Polish Academy of Sciences
- Semmelweis University
- Vadaskert Child and Adolescent Psychiatric Hospital
- Icahn School of Medicine at Mount Sinai
- Radboud University Nijmegen
- deCODE Genetics
- Boehringer Ingelheim GmbH
- Aristotle University of Thessaloniki
- University of Washington
- Altius Institute for Biomedical Sciences
- Tel Aviv University
- University of Rome La Sapienza
- King's College London (KCL)
- Great Ormond Street Hospital for Children NHS Trust
- Levvel Academic Center for Child and Adolescent Psychiatry
- Amsterdam University Medical Centers (UMC)
- Hospital Universitario Virgen del Rocio
- CIBER - Center for Biomedical Research Network
- University of Barcelona
- August Pi i Sunyer Biomedical Research Institute
- Ludwig Maximilian University of Munich
- University of Lübeck
- University of Lausanne
- ASL BA
- University of Zurich
- University College London
- University of Calgary
Abstract
Background: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year. Methods: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants. Results: We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume. Conclusions: Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies.
Details
Original language | English |
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Pages (from-to) | 114-124 |
Number of pages | 11 |
Journal | Biological psychiatry |
Volume | 96 |
Issue number | 2 |
Publication status | Published - 15 Jul 2024 |
Peer-reviewed | Yes |
External IDs
PubMed | 36738982 |
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Mendeley | efc0ac3a-941d-3c03-ac69-c951489375e8 |
Keywords
ASJC Scopus subject areas
Keywords
- GWAS, Meta-analysis, NR2F1, Tourette syndrome