Genome-wide Association Study points to novel locus for Gilles de la Tourette Syndrome

Fotis Tsetsos, Apostolia Topaloudi, Pritesh Jain, Zhiyu Yang, Dongmei Yu, Petros Kolovos, Zeynep Tumer, Renata Rizzo, Andreas Hartmann, Christel Depienne, Yulia Worbe, Kirsten R Müller-Vahl, Danielle C Cath, Dorret I Boomsma, Tomasz Wolanczyk, Cezary Zekanowski, Csaba Barta, Zsofia Nemoda, Zsanett Tarnok, Shanmukha S PadmanabhuniJoseph D Buxbaum, Dorothy Grice, Jeffrey Glennon, Hreinn Stefansson, Bastian Hengerer, Evangelia Yannaki, John A Stamatoyannopoulos, Noa Benaroya-Milshtein, Francesco Cardona, Tammy Hedderly, Isobel Heyman, Chaim Huyser, Pablo Mir, Astrid Morer, Norbert Mueller, Alexander Munchau, Kerstin J Plessen, Cesare Porcelli, Veit Roessner, Susanne Walitza, Anette Schrag, Davide Martino, Jay A Tischfield, Gary A Heiman, A Jeremy Willsey, Andrea Dietrich, Lea K Davis, James J Crowley, Carol A Mathews, Jeremiah M Scharf*, PGC TS Working Group

*Corresponding author for this work
3 Citations (Scopus)


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.

Original languageEnglish
JournalBiological Psychiatry
Publication statusE-pub ahead of print - 2 Feb 2023


  • GWAS
  • Meta-analysis
  • NR2F1
  • Tourette syndrome


Dive into the research topics of 'Genome-wide Association Study points to novel locus for Gilles de la Tourette Syndrome'. Together they form a unique fingerprint.

Cite this