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

The PGC TS Working Group; The TSAICG; The TSGeneSEE Initiative; the EMTICS Collaborative Group; The TS-EUROTRAIN Network; The TIC Genetics Collaborative Group

doi:10.1016/j.biopsych.2023.01.023

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

The PGC TS Working Group, The TSAICG, The TSGeneSEE Initiative, the EMTICS Collaborative Group, The TS-EUROTRAIN Network, The TIC Genetics Collaborative Group

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English
Pages (from-to)	114-124
Number of pages	11
Journal	Biological Psychiatry
Volume	96
Issue number	2
DOIs	https://doi.org/10.1016/j.biopsych.2023.01.023
State	Published - 15 Jul 2024

Funding

Funders	Funder number
Tourette Association of America
Parkinson Canada
Stichting VC-GGZ
Ipsen Corporate
Weill Institute for Neurosciences, University of California, San Francisco
Emberi Eroforrások Minisztériuma
Boehringer Ingelheim
Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional
TSAA
Dystonia Medical Research Foundation Canada
Semmelweis Egyetem
New Jersey Center for Tourette Syndrome and Associated Disorders
TS-EUROTRAIN
Michael P. Smith Family
National Science Center, Poland
NIHR UCL
Owerko Foundation
Manchester Biomedical Research Centre
Michael P Smith Family
New Jersey Center for Tourette Syndrome and Associated Disorder
ISCIII-FEDER	PI16/01575, PI19/01576
Consejería de Salud y Bienestar Social, Junta de Andalucía	PE-0210-2018
EMTICS	278367, FP7-HEALTH
National Institutes of Health	MH115958, MH115959, MH115963, R01NS102371, MH115993, MH115960, MH115961, MH115962
Magyar Tudományos Akadémia	UNKP-18-4, BO/00987/16/5, /00987/16/5
National Science Foundation	2006929, 1715202
Ministerio de Ciencia e Innovación	RTC2019-007150-1
Narodowe Centrum Nauki	UMO-2016/23/B/NZ2/03030
National Institute of Mental Health	R01MH126213
TSEUROTRAIN	316978, FP7-PEOPLE
Junta de Andalucía	CTS-7685, CVI-02526
Deutsche Forschungsgemeinschaft	FOR 2698
Lundbeck Fonden	R100-2011-9332
National Institute of Neurological Disorders and Stroke	R01NS105746

Keywords

GWAS
Meta-analysis
NR2F1
Tourette syndrome

Access to Document

10.1016/j.biopsych.2023.01.023

Cite this

@article{bb462c5f599d49148892299fe2b9e31c,

title = "Genome-Wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome",

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.",

keywords = "GWAS, Meta-analysis, NR2F1, Tourette syndrome",

author = "{The PGC TS Working Group} and {The TSAICG} and {The TSGeneSEE Initiative} and {the EMTICS Collaborative Group} and {The TS-EUROTRAIN Network} and {The TIC Genetics Collaborative Group} and Fotis Tsetsos and Apostolia Topaloudi and Pritesh Jain and Zhiyu Yang and Dongmei Yu and Petros Kolovos and Zeynep Tumer and Renata Rizzo and Andreas Hartmann and Christel Depienne and Yulia Worbe and M{\"u}ller-Vahl, {Kirsten R.} and Cath, {Danielle C.} and Boomsma, {Dorret I.} and Tomasz Wolanczyk and Cezary Zekanowski and Csaba Barta and Zsofia Nemoda and Zsanett Tarnok and Padmanabhuni, {Shanmukha S.} and Buxbaum, {Joseph D.} and Dorothy Grice and Jeffrey Glennon and Hreinn Stefansson and Bastian Hengerer and Evangelia Yannaki and Stamatoyannopoulos, {John A.} and Noa Benaroya-Milshtein and Francesco Cardona and Tammy Hedderly and Isobel Heyman and Chaim Huyser and Pablo Mir and Astrid Morer and Norbert Mueller and Alexander Munchau and Plessen, {Kerstin J.} and Cesare Porcelli and Veit Roessner and Susanne Walitza and Anette Schrag and Davide Martino and Barr, {Cathy L.} and Batterson, {James R.} and Cheston Berlin and Budman, {Cathy L.} and Giovanni Coppola and Cox, {Nancy J.} and Alan Apter and Tamar Steinberg",

note = "Publisher Copyright: {\textcopyright} 2023 Society of Biological Psychiatry",

year = "2024",

month = jul,

day = "15",

doi = "10.1016/j.biopsych.2023.01.023",

language = "אנגלית",

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AU - The PGC TS Working Group

AU - The TSAICG

AU - The TSGeneSEE Initiative

AU - the EMTICS Collaborative Group

AU - The TS-EUROTRAIN Network

AU - The TIC Genetics Collaborative Group

AU - Tsetsos, Fotis

AU - Topaloudi, Apostolia

AU - Jain, Pritesh

AU - Yang, Zhiyu

AU - Yu, Dongmei

AU - Kolovos, Petros

AU - Tumer, Zeynep

AU - Rizzo, Renata

AU - Hartmann, Andreas

AU - Depienne, Christel

AU - Worbe, Yulia

AU - Müller-Vahl, Kirsten R.

AU - Cath, Danielle C.

AU - Boomsma, Dorret I.

AU - Wolanczyk, Tomasz

AU - Zekanowski, Cezary

AU - Barta, Csaba

AU - Nemoda, Zsofia

AU - Tarnok, Zsanett

AU - Padmanabhuni, Shanmukha S.

AU - Buxbaum, Joseph D.

AU - Grice, Dorothy

AU - Glennon, Jeffrey

AU - Stefansson, Hreinn

AU - Hengerer, Bastian

AU - Yannaki, Evangelia

AU - Stamatoyannopoulos, John A.

AU - Benaroya-Milshtein, Noa

AU - Cardona, Francesco

AU - Hedderly, Tammy

AU - Heyman, Isobel

AU - Huyser, Chaim

AU - Mir, Pablo

AU - Morer, Astrid

AU - Mueller, Norbert

AU - Munchau, Alexander

AU - Plessen, Kerstin J.

AU - Porcelli, Cesare

AU - Roessner, Veit

AU - Walitza, Susanne

AU - Schrag, Anette

AU - Martino, Davide

AU - Barr, Cathy L.

AU - Batterson, James R.

AU - Berlin, Cheston

AU - Budman, Cathy L.

AU - Coppola, Giovanni

AU - Cox, Nancy J.

AU - Apter, Alan

AU - Steinberg, Tamar

PY - 2024/7/15

Y1 - 2024/7/15

N2 - 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.

AB - 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.

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KW - Meta-analysis

KW - NR2F1

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ER -

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

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Keywords

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