Genome-wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • The PGC TS Working Group - (Author)
  • The TSAICG - (Author)
  • The TSGeneSEE Initiative - (Author)
  • The EMTICS collaborative group - (Author)
  • The TS-EUROTRAIN Network - (Author)
  • The TIC Genetics Collaborative Group - (Author)
  • 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 languageEnglish
Pages (from-to)114-124
Number of pages11
JournalBiological psychiatry
Volume96
Issue number2
Publication statusPublished - 15 Jul 2024
Peer-reviewedYes

External IDs

PubMed 36738982
Mendeley efc0ac3a-941d-3c03-ac69-c951489375e8

Keywords

ASJC Scopus subject areas

Keywords

  • GWAS, Meta-analysis, NR2F1, Tourette syndrome