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 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; TSAICG; Barbara Jane Coffey

doi:10.1016/j.biopsych.2023.01.023

Back

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

Journal article

Peer reviewed

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, …

Biological psychiatry (1969), Vol.96(2), pp.114-124

2024-07-15

DOI: https://doi.org/10.1016/j.biopsych.2023.01.023

PMID: 36738982

Appears in Miller School of Medicine - Latest Publications

Abstract

Adolescent

Brain - diagnostic imaging

Brain - pathology

Child

Chromosomes, Human, Pair 5 - genetics

Female

Genetic Predisposition to Disease

Genome-Wide Association Study

Humans

Male

Putamen - diagnostic imaging

Quantitative Trait Loci

RNA, Long Noncoding - genetics

Tourette Syndrome - genetics

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. 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. 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. Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies.

Metrics

1 Record Views

See more details

Details

Title: Genome-Wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome
Creators: Fotis Tsetsos - Democritus University of Thrace
Apostolia Topaloudi - Purdue University West Lafayette
Pritesh Jain - Purdue University West Lafayette
Zhiyu Yang - Purdue University West Lafayette
Dongmei Yu - Broad Institute
Petros Kolovos - Democritus University of Thrace
Zeynep Tumer - Copenhagen University Hospital
Renata Rizzo - University of Catania
Andreas Hartmann - Pitié-Salpêtrière Hospital
Christel Depienne - Essen University Hospital
Yulia Worbe - Sorbonne Université
Kirsten R Müller-Vahl - Medizinische Hochschule Hannover
Danielle C Cath - Utrecht University
Dorret I Boomsma - Amsterdam Public Health
Tomasz Wolanczyk - Medical University of Warsaw
Cezary Zekanowski - Polish Academy of Sciences
Csaba Barta - Institute of Biochemistry
Zsofia Nemoda - Institute of Biochemistry
Zsanett Tarnok - Vadaskert Alapítvány a Gyermekek Lelki Egészségéért
Shanmukha S Padmanabhuni - Purdue University West Lafayette
Joseph D Buxbaum - Icahn School of Medicine at Mount Sinai
Dorothy Grice - Icahn School of Medicine at Mount Sinai
Jeffrey Glennon - Radboud University Nijmegen
Hreinn Stefansson - deCODE Genetics
Bastian Hengerer - Boehringer Ingelheim
Evangelia Yannaki - G. Papanikolaou General Hospital
John A Stamatoyannopoulos - University of Washington
Noa Benaroya-Milshtein - Schneider Children's Medical Center
Francesco Cardona - Sapienza University of Rome
Tammy Hedderly - Kings Health Partners
Isobel Heyman - Great Ormond Street Hospital for Children NHS Foundation Trust
Chaim Huyser - Amsterdam University Medical Centers
Pablo Mir - Hospital Universitario Virgen del Rocío
Astrid Morer - Instituto de Salud Carlos III
Norbert Mueller - LMU Klinikum
Alexander Munchau - University of Lübeck
Kerstin J Plessen - Mental Health Services
Cesare Porcelli - British Science Association
Veit Roessner - Technische Universität Dresden
Susanne Walitza - University of Zurich
Anette Schrag - University College London
Davide Martino - University of Calgary
Jay A Tischfield - Rutgers, The State University of New Jersey
Gary A Heiman - Rutgers, The State University of New Jersey
A Jeremy Willsey - University of California, San Francisco
Andrea Dietrich - University Medical Center Groningen
Lea K Davis - Vanderbilt University Medical Center
James J Crowley - University of North Carolina at Chapel Hill
Carol A Mathews - Florida College
Jeremiah M Scharf - Massachusetts General Hospital
Marianthi Georgitsi - Aristotle University of Thessaloniki
Pieter J Hoekstra - University Medical Center Groningen
Peristera Paschou - Purdue University West Lafayette
TSAICG
Barbara Jane Coffey - UMMG Dept of Psychiatry & Behavioral Sciences
Publication Details: Biological psychiatry (1969), Vol.96(2), pp.114-124
Grant note: R01 NS102371 / NINDS NIH HHS R01 MH115959 / NIMH NIH HHS R01 MH115963 / NIMH NIH HHS U24 NS095914 / NINDS NIH HHS R01 MH115961 / NIMH NIH HHS R01 NS105746 / NINDS NIH HHS R01 MH115993 / NIMH NIH HHS R01 MH115960 / NIMH NIH HHS K02 NS085048 / NINDS NIH HHS R01 MH126213 / NIMH NIH HHS
Academic Unit: Miller School of Medicine; UMMG Dept of Psychiatry & Behavioral Sciences
Language: English
Resource Type: Journal article
PMID: 36738982
Record Identifier: 991032796084302976