Concordance of genetic variation that increases risk for Tourette Syndrome and that influences its underlying neurocircuitry

Mary Mufford; Josh Cheung; Neda Jahanshad; Celia van der Merwe; Linda Ding; Nynke Groenewold; Nastassja Koen; Emile R Chimusa; Shareefa Dalvie; Raj Ramesar; James A Knowles; Christine Lochner; Derrek P Hibar; Peristera Paschou; Odile A van den Heuvel; Sarah E Medland; Jeremiah M Scharf; Carol A Mathews; Paul M Thompson; Dan J Stein; Gil Atzmon; Cathy Barr; Csaba Barta; Robert Batterson; Fortu Benarroch; Chester Berlin; Gabriel Berrio; Julia Bohnenpoll; Lawrence Brown; Ruth Bruun; Randy Buckner; Cathy Budman; Julio Cardona Silgado; Danielle Cath; Keun-Ah Cheon; Sylvain Chouinard; Barbara Coffey; Giovanni Coppola; Nancy Cox; Sabrina Darrow; Lea Davis; Christel Depienne; Andrea Dietrich; Yves Dion; Valsamma Eapen; Lonneke Elzerman; Thomas Fernandez; Nelson Freimer; Odette Fründt; Blanca Garcia-Delgar; Donald Gilbert; Marco Grados; Erica Greenberg; Dorothy Grice; Varda Gross-Tsur; Julie Hagstrøm; Andreas Hartmann; Johannes Hebebrand; Tammy Hedderly; Gary Heiman; Luis Herrera; Isobel Heyman; Matthew Hirschtritt; Pieter Hoekstra; Hyun Ju Hong; Alden Huang; Chaim Huyser; Laura Ibanez-Gomez; Cornelia Illmann; Joseph Jankovic; Judith Kidd; Kenneth Kidd; Young Key Kim; Young-Shin Kim; Robert King; Yun-Joo Koh; Anastasios Konstantinidis; Sodahm Kook; Samuel Kuperman; Roger Kurlan; James Leckman; Paul C. Lee; Bennett Leventhal; Thomas Lowe; Andrea Ludolph; Claudia Lührs Da Silva; Gholson Lyon; Marcos Madruga-Garrido; Irene Malaty; Athanasios Maras; Carol A. Mathews; William Mcmahon; Sandra Mesa Restrepo; Pablo Mir; Astrid Morer; Kirsten Müller-Vahl; Alexander Münchau; Tara Murphy; Allan Naarden; Peter Nagy; Benjamin Neale; Markus Noethen; William Ochoa; Michael Okun; Lisa Osiecki; Peristera Paschou; David Pauls; Christopher Pittenger; Kerstin Plessen; Yehuda Pollak; Danielle Posthuma; Eliana Ramos; Victor Reus; Renata Rizzo; Mary Robertson; Veit Roessner; Josh Roffman; Guy Rouleau; Andres Ruiz-Linares; Paul Sandor; Jeremiah Scharf; Monika Schlögelhofer; Eun-Young Shin; Harvey Singer; Jan Smit; Jordan Smoller; Dong-Ho Song; Jungeun Song; Mara Stamenkovic; Matthew State; Manfred Stuhrmann; Jae-Hoon Sul; Urszula Szymanska; Zsanett Tarnok; Jay Tischfield; Fotis Tsetsos; Jennifer Tübing; Ana Valencia Duarte; Frank Visscher; Sina Wanderer; Tomasz Wolanczyk; Martin Woods; Yulia Worbe; Dongmei Yu; Ivette Zelaya; Samuel Zinner. Enigma

doi:10.1038/s41398-019-0452-3

Journal Articles Translational Psychiatry Year : 2019

Concordance of genetic variation that increases risk for Tourette Syndrome and that influences its underlying neurocircuitry

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Mary Mufford

Function : Author
PersonId : 1349149
ORCID : 0000-0002-8409-9217

University of Cape Town

Josh Cheung

Function : Author

Southern California University of Health Sciences

Neda Jahanshad

Function : Author

Southern California University of Health Sciences

Celia van der Merwe

Function : Author

University of Cape Town

Linda Ding

Function : Author

Southern California University of Health Sciences

Nynke Groenewold

Function : Author

University of Cape Town

Nastassja Koen

Function : Author

University of Cape Town

Emile R Chimusa

Function : Author
PersonId : 1349150
ORCID : 0000-0001-8846-2047

University of Cape Town

Shareefa Dalvie

Function : Author

University of Cape Town

Raj Ramesar

Function : Author

University of Cape Town

James A Knowles

Function : Author

Southern California University of Health Sciences

Christine Lochner

Function : Author

Institute for Wine Biotechnology [University of Stellenbosch - Afrique du Sud]

Derrek P Hibar

Function : Author

Southern California University of Health Sciences

Peristera Paschou

Function : Author

Purdue University [West Lafayette]

Odile A van den Heuvel

Function : Author

VU University Medical Center [Amsterdam]

Sarah E Medland

Function : Author

QIMR Berghofer Medical Research Institute

Jeremiah M Scharf

Function : Author

Harvard Medical School [Boston]

Carol A Mathews

Function : Author

University of Florida [Gainesville]

Paul M Thompson

Function : Author

Southern California University of Health Sciences

Dan J Stein

Function : Author
PersonId : 1349151

University of Cape Town

Gil Atzmon

Function : Author

Cathy Barr

Function : Author

Csaba Barta

Function : Author

Robert Batterson

Function : Author

Fortu Benarroch

Function : Author

Chester Berlin

Function : Author

Gabriel Berrio

Function : Author

Julia Bohnenpoll

Function : Author

Lawrence Brown

Function : Author

Ruth Bruun

Function : Author

Randy Buckner

Function : Author

Cathy Budman

Function : Author

Julio Cardona Silgado

Function : Author

Danielle Cath

Function : Author

Keun-Ah Cheon

Function : Author

Sylvain Chouinard

Function : Author

Barbara Coffey

Function : Author

Giovanni Coppola

Function : Author

Nancy Cox

Function : Author

Sabrina Darrow

Function : Author

Lea Davis

Function : Author

Christel Depienne

Function : Author

Institut du Cerveau = Paris Brain Institute

Andrea Dietrich

Function : Author

Yves Dion

Function : Author

Valsamma Eapen

Function : Author

Lonneke Elzerman

Function : Author

Thomas Fernandez

Function : Author

Nelson Freimer

Function : Author

Odette Fründt

Function : Author

Blanca Garcia-Delgar

Function : Author

Donald Gilbert

Function : Author

Marco Grados

Function : Author

Erica Greenberg

Function : Author

Dorothy Grice

Function : Author

Varda Gross-Tsur

Function : Author

Julie Hagstrøm

Function : Author

Andreas Hartmann

Function : Author

Institut du Cerveau = Paris Brain Institute

Johannes Hebebrand

Function : Author

Tammy Hedderly

Function : Author

Gary Heiman

Function : Author

Luis Herrera

Function : Author

Isobel Heyman

Function : Author

Matthew Hirschtritt

Function : Author

Pieter Hoekstra

Function : Author

Hyun Ju Hong

Function : Author

Alden Huang

Function : Author

Chaim Huyser

Function : Author

Laura Ibanez-Gomez

Function : Author

Cornelia Illmann

Function : Author

Joseph Jankovic

Function : Author

Judith Kidd

Function : Author

Kenneth Kidd

Function : Author

Young Key Kim

Function : Author

Young-Shin Kim

Function : Author

Robert King

Function : Author

Yun-Joo Koh

Function : Author

Anastasios Konstantinidis

Function : Author

Sodahm Kook

Function : Author

Samuel Kuperman

Function : Author

Roger Kurlan

Function : Author

James Leckman

Function : Author

Paul C. Lee

Function : Author

Bennett Leventhal

Function : Author

Thomas Lowe

Function : Author

Andrea Ludolph

Function : Author

Claudia Lührs Da Silva

Function : Author

Gholson Lyon

Function : Author

Marcos Madruga-Garrido

Function : Author

Irene Malaty

Function : Author

Athanasios Maras

Function : Author

Carol A. Mathews

Function : Author

William Mcmahon

Function : Author

Sandra Mesa Restrepo

Function : Author

Pablo Mir

Function : Author

Astrid Morer

Function : Author

Kirsten Müller-Vahl

Function : Author

Alexander Münchau

Function : Author

Tara Murphy

Function : Author

Allan Naarden

Function : Author

Peter Nagy

Function : Author

Benjamin Neale

Function : Author

Markus Noethen

Function : Author

William Ochoa

Function : Author

Michael Okun

Function : Author

Lisa Osiecki

Function : Author

Peristera Paschou

Function : Author

David Pauls

Function : Author

Christopher Pittenger

Function : Author

Kerstin Plessen

Function : Author

Yehuda Pollak

Function : Author

Danielle Posthuma

Function : Author

Eliana Ramos

Function : Author

Victor Reus

Function : Author

Renata Rizzo

Function : Author

Mary Robertson

Function : Author

Veit Roessner

Function : Author

Josh Roffman

Function : Author

Guy Rouleau

Function : Author

Andres Ruiz-Linares

Function : Author

Paul Sandor

Function : Author

Jeremiah Scharf

Function : Author

Monika Schlögelhofer

Function : Author

Eun-Young Shin

Function : Author

Harvey Singer

Function : Author

Jan Smit

Function : Author

Jordan Smoller

Function : Author

Dong-Ho Song

Function : Author

Jungeun Song

Function : Author

Mara Stamenkovic

Function : Author

Matthew State

Function : Author

Manfred Stuhrmann

Function : Author

Jae-Hoon Sul

Function : Author

Urszula Szymanska

Function : Author

Zsanett Tarnok

Function : Author

Jay Tischfield

Function : Author

Fotis Tsetsos

Function : Author

Jennifer Tübing

Function : Author

Ana Valencia Duarte

Function : Author

Frank Visscher

Function : Author

Sina Wanderer

Function : Author

Tomasz Wolanczyk

Function : Author

Martin Woods

Function : Author

Yulia Worbe

Function : Author

Institut du Cerveau = Paris Brain Institute

Dongmei Yu

Function : Author

Ivette Zelaya

Function : Author

Samuel Zinner. Enigma

Function : Author

Abstract

There have been considerable recent advances in understanding the genetic architecture of Tourette Syndrome (TS) as well as its underlying neurocircuitry. However, the mechanisms by which genetic variation that increases risk for TS—and its main symptom dimensions—influence relevant brain regions are poorly understood. Here we undertook a genome-wide investigation of the overlap between TS genetic risk and genetic influences on the volume of specific subcortical brain structures that have been implicated in TS. We obtained summary statistics for the most recent TS genome-wide association study (GWAS) from the TS Psychiatric Genomics Consortium Working Group (4644 cases and 8695 controls) and GWAS of subcortical volumes from the ENIGMA consortium (30,717 individuals). We also undertook analyses using GWAS summary statistics of key symptom factors in TS, namely social disinhibition and symmetry behaviour. SNP effect concordance analysis (SECA) was used to examine genetic pleiotropy—the same SNP affecting two traits—and concordance—the agreement in single nucelotide polymorphism (SNP) effect directions across these two traits. In addition, a conditional false discovery rate (FDR) analysis was performed, conditioning the TS risk variants on each of the seven subcortical and the intracranial brain volume GWAS. Linkage disequilibrium score regression (LDSR) was used as validation of the SECA method. SECA revealed significant pleiotropy between TS and putamen ( p = 2 × 10 −4 ) and caudate ( p = 4 × 10 −4 ) volumes, independent of direction of effect, and significant concordance between TS and lower thalamic volume ( p = 1 × 10 −3 ). LDSR lent additional support for the association between TS and thalamus volume ( p = 5.85 × 10 −2 ). Furthermore, SECA revealed significant evidence of concordance between the social disinhibition symptom dimension and lower thalamus volume ( p = 1 × 10 −3 ), as well as concordance between symmetry behaviour and greater putamen volume ( p = 7 × 10 −4 ). Conditional FDR analysis further revealed novel variants significantly associated with TS ( p < 8 × 10 −7 ) when conditioning on intracranial (rs2708146, q = 0.046; and rs72853320, q = 0.035) and hippocampal (rs1922786, q = 0.001) volumes, respectively. These data indicate concordance for genetic variation involved in disorder risk and subcortical brain volumes in TS. Further work with larger samples is needed to fully delineate the genetic architecture of these disorders and their underlying neurocircuitry.

Domains

Human health and pathology

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https://hal.sorbonne-universite.fr/hal-04446196

Submitted on : Thursday, February 8, 2024-11:26:06 AM

Last modification on : Friday, February 9, 2024-3:39:56 AM

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hal-04446196 , version 1 (08-02-2024)

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HAL Id : hal-04446196 , version 1
DOI : 10.1038/s41398-019-0452-3
PUBMED : 30902966
PUBMEDCENTRAL : PMC6430767

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Mary Mufford, Josh Cheung, Neda Jahanshad, Celia van der Merwe, Linda Ding, et al.. Concordance of genetic variation that increases risk for Tourette Syndrome and that influences its underlying neurocircuitry. Translational Psychiatry, 2019, 9 (1), pp.120. ⟨10.1038/s41398-019-0452-3⟩. ⟨hal-04446196⟩

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Concordance of genetic variation that increases risk for Tourette Syndrome and that influences its underlying neurocircuitry

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