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

PGC TS Working Group, TSAICG, TSGeneSEE initiative, EMTICS Collaborative Group, TS-EUROTRAIN network, TIC Genetics collaborative group, 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 BoomsmaTomasz Wolanczyk, Cezary Zekanowski, Csaba Barta, Zsofia Nemoda, Zsanett Tarnok, Shanmukha S Padmanabhuni, Joseph 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, Marianthi Georgitsi, Pieter J Hoekstra*, Peristera Paschou*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review


BACKGROUND: Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture, characterized by multiple motor tics and at least one vocal tic persisting for more than one year.

METHODS: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6,133 TS individuals and 13,565 ancestry-matched controls.

RESULTS: We identified a genome-wide significant locus on chromosome 5q15. Integration of eQTL, Hi-C and GWAS data implicated the NR2F1 gene and associated lncRNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring on brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume.

CONCLUSIONS: Our work presents novel insights in the neurobiology of TS opening up new directions for future studies.

Originele taal-2English
TijdschriftBiological Psychiatry
StatusE-pub ahead of print - 2-feb.-2023

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