Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome - Sorbonne Université Access content directly
Journal Articles Translational Psychiatry Year : 2023

Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

Pritesh Jain (1) , Tyne Miller-Fleming (2) , Apostolia Topaloudi (1) , Dongmei Yu (3) , Petros Drineas (1) , Marianthi Georgitsi (4) , Zhiyu Yang (1) , Renata Rizzo (5) , Kirsten R Müller-Vahl (6) , Zeynep Tumer (7) , Nanette Mol Debes , Andreas Hartmann (8) , Christel Depienne (9) , Yulia Worbe (8) , Pablo Mir (10) , Danielle C Cath (11) , Dorret I Boomsma (12) , Veit Roessner (13) , Tomasz Wolanczyk (14) , Piotr Janik (14) , Natalia Szejko (14) , Cezary Zekanowski (15) , Csaba Barta (16) , Zsofia Nemoda (16) , Zsanett Tarnok , Joseph D Buxbaum , Dorothy Grice , Jeffrey Glennon , Hreinn Stefansson , Bastian Hengerer , Noa Benaroya-Milshtein , Francesco Cardona , Tammy Hedderly , Isobel Heyman , Chaim Huyser , Astrid Morer , Norbert Mueller , Alexander Munchau , Kerstin J Plessen , Cesare Porcelli , Susanne Walitza , Anette Schrag , Davide Martino , Thomas D Als , Harald Aschauer , Gil Atzmon , Matie Bækvad-Hansen , Csaba Barta , Cathy L Barr , Nir Barzilai , James R Batterson , Robert Batterson , Fortu Benarroch , Cheston Berlin , Julia Boberg , Benjamin Bodmer , Julia Bohnenpoll , Anders D Børglum , Lawrence W Brown , Ruth Bruun , Cathy L Budman , Randy L Buckner , Joseph D Buxbaum , Jonas Bybjerg-Grauholm , Danielle C Cath , Keun-Ah Cheon , Sylvain Chouinard , Barbara J Coffey , Giovanni Coppola , James J Crowley , Niklas Dahl , Lea K Davis , Sabrina M Darrow , Mark J Daly , Christel Depienne , Silvia De Rubeis , Andrea Dietrich , Yves Dion , Diana R Djurfeldt , Laura Domenech-Salgado , Valsamma Eapen , Lonneke Elzerman , Thomas V Fernandez , Nelson B Freimer Carolin Fremer , Blanca Garcia-Delgar , Marcos Garrido , Donald L Gilbert , Paola Giusti-Rodriguez , Marco Grados , Erica Greenberg , Jakob Grove , Dorothy E Grice , Julie Hagstrom , Matt Halvorsen , Andreas Hartmann , Bjarne Hansen , Jan Haavik , Johannes Hebebrand , Gary A Heiman , Luis Herrera , Isobel Heyman , Anke Hinney , Matthew E Hirschtritt , Pieter J Hoekstra , Jae Hoon Sul , Hyun Ju Hong , David M Hougaard , Alden Y Huang , Laura Ibanez-Gomez , Franjo Ivankovic , Joseph Jankovic , Elinor K Karlsson , Jakko A Kaprio , Young Key Kim , Young-Shin Kim , Robert A King , James A Knowles , Yun-Joo Koh , Sodham Kook , Najah Khalifa , Anastasios Konstantinidis , Samuel Kuperman , Roger Kurlan , Gerd Kvale , James Leckman , Paul C Lee , Bennett Leventhal , Paul Lichtenstein , Kerstin Lindbald-Toh , Thomas Lowe , Andrea Ludolph , Claudia Luhrs da Silva , Pétur Luðvigsson , Jurjen Luykx , Gholson J Lyon , Behrang Mahjani , Athanasios Maras , David Mataix-Cols , Manuel Mattheisen , Carol A Mathews , Irene A Malaty , William M Mcmahon , Andrew Mcquillin , Sandra M Meier , Tyne Miller-Fleming , Pablo Mir , Rainald Moessner , Astrid Morer , Preben B Mortensen , Ole Mors , Poorva Mudgal , Kirsten R Muller-Vahl , Alexander Munchau , Peter Nagy , Allan Naarden , Benjamin M Neale , Muhammad S Nawaz , Judith Becker Nissen , Markus M Nöthen Merete Nordentoft , Ashley E Nordsletten , Michael S Okun , Roel Ophoff , Lisa Osiecki , Aarno Palotie , Teemu P Palviainen , Peristera Paschou (1) , Carlos N Pato Michele T. Pato , Christopher Pittenger , Kerstin J Plessen , Yehuda Pollak , Danielle Posthuma , Eliana Ramos , Jennifer Reichert , Renata Rizzo , Mary M Robertson , Veit Roessner , Joshua L Roffman , Guy Rouleau , Christian Rück , Evald Sæmundsen , Jack Samuels , Sven Sandin , Paul Sandor , Monika Schlögelhofer , Jeremiah M Scharf , Eun-Young Shin , Harvey S Singer , Jan Smit , Jordan W Smoller , Matthew State , Stian Solem , Dong-Ho Song , Jungeun Song , Mara Stamenkovic , Hreinn Stefansson , Kári Stefansson , Nora Strom , Manfred Stuhrmann , Jin Szatkiewicz , Urszula Szymanska , Zsanett Tarnok , Jay A Tischfield , Fotis Tsetsos , Ólafur Thorarensen , Jennifer Tubing , Frank Visscher , Michael Wagner , Sina Wanderer , Sheng Wang , Thomas Werge , Jeremy A Willsey , Tomasz Wolancyk , Douglas W Woods , Martin Woods , Yulia Worbe , Yves Dion , Dongmei Yu , Ivette Zelaya , Samuel H Zinner , Alan Apter , Juliane Ball , Benjamin Bodmer , Emese Bognar , Judith Buse , Marta Correa Vela , Carolin Fremer , Blanca Garcia-Delgar , Mariangela Gulisano , Annelieke Hagen , Julie Hagstrøm , Marcos Madruga-Garrido , Peter Nagy , Alessandra Pellico , Daphna Ruhrman , Jaana Schnell , Paola Rosaria Silvestri , Liselotte Skov , Tamar Steinberg , Friederike Tagwerker Gloor , Victoria L Turner , Elif Weidinger , Noa Benaroya-Milshtein , Francesco Cardona , Andrea Dietrich , Marianthi Georgitsi , Tammy Hedderly , Isobel Heyman , Pieter J Hoekstra , Chaim Huyser , Davide Martino , Pablo Mir , Astrid Morer , Kirsten R Muller-Vahl , Peristera Paschou , Kerstin J Plessen , Cesare Porcelli , Renata Rizzo , Veit Roessner , Anette Schrag , Zsanett Tarnok , Andrea Dietrich , John Alexander , Tamas Aranyi , Wim R Buisman , Jan K Buitelaar , Nicole Driessen , Petros Drineas , Siyan Fan , Natalie J Forde , Sarah Gerasch , Odile A van den Heuvel , Cathrine Jespersgaard , Ahmad S Kanaan , Harald E Möller , Muhammad S Nawaz , Ester Nespoli , Luca Pagliaroli , Geert Poelmans , Petra J W Pouwels , Francesca Rizzo , Dick J Veltman , Ysbrand D van der Werf , Joanna Widomska , Nuno R Zilhäo , Csaba Barta , Dorret I Boomsma , Danielle C Cath , Marianthi Georgitsi , Jeffrey Glennon , Bastian Hengerer , Pieter J Hoekstra , Kirsten R Muller-Vahl , Peristera Paschou , Hreinn Stefansson , Zeynep Tumer , Carol A Mathews , Jeremiah M Scharf , Pieter J Hoekstra , Lea K Davis , Peristera Paschou
Nanette Mol Debes
  • Function : Author
Christel Depienne
Zsanett Tarnok
Joseph D Buxbaum
Dorothy Grice
  • Function : Author
Jeffrey Glennon
  • Function : Author
Hreinn Stefansson
  • Function : Author
Bastian Hengerer
Noa Benaroya-Milshtein
  • Function : Author
Francesco Cardona
  • Function : Author
Tammy Hedderly
Isobel Heyman
  • Function : Author
Chaim Huyser
Astrid Morer
  • Function : Author
Norbert Mueller
  • Function : Author
Alexander Munchau
  • Function : Author
Kerstin J Plessen
  • Function : Author
Cesare Porcelli
  • Function : Author
Susanne Walitza
  • Function : Author
Anette Schrag
  • Function : Author
Davide Martino
  • Function : Author
Thomas D Als
  • Function : Author
Harald Aschauer
  • Function : Author
Gil Atzmon
  • Function : Author
Matie Bækvad-Hansen
  • Function : Author
Csaba Barta
  • Function : Author
Cathy L Barr
  • Function : Author
Nir Barzilai
  • Function : Author
James R Batterson
  • Function : Author
Robert Batterson
  • Function : Author
Fortu Benarroch
  • Function : Author
Cheston Berlin
  • Function : Author
Julia Boberg
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Benjamin Bodmer
  • Function : Author
Julia Bohnenpoll
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Anders D Børglum
  • Function : Author
Lawrence W Brown
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Ruth Bruun
  • Function : Author
Cathy L Budman
  • Function : Author
Randy L Buckner
  • Function : Author
Joseph D Buxbaum
  • Function : Author
Jonas Bybjerg-Grauholm
  • Function : Author
Danielle C Cath
  • Function : Author
Keun-Ah Cheon
  • Function : Author
Sylvain Chouinard
  • Function : Author
Barbara J Coffey
  • Function : Author
Giovanni Coppola
  • Function : Author
James J Crowley
  • Function : Author
Niklas Dahl
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Lea K Davis
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Sabrina M Darrow
  • Function : Author
Mark J Daly
  • Function : Author
Christel Depienne
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Silvia De Rubeis
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Andrea Dietrich
  • Function : Author
Yves Dion
  • Function : Author
Diana R Djurfeldt
  • Function : Author
Laura Domenech-Salgado
  • Function : Author
Valsamma Eapen
  • Function : Author
Lonneke Elzerman
  • Function : Author
Thomas V Fernandez
  • Function : Author
Blanca Garcia-Delgar
  • Function : Author
Marcos Garrido
  • Function : Author
Donald L Gilbert
  • Function : Author
Paola Giusti-Rodriguez
  • Function : Author
Marco Grados
  • Function : Author
Erica Greenberg
  • Function : Author
Jakob Grove
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Dorothy E Grice
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Julie Hagstrom
  • Function : Author
Matt Halvorsen
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Andreas Hartmann
  • Function : Author
Bjarne Hansen
  • Function : Author
Jan Haavik
  • Function : Author
Johannes Hebebrand
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Gary A Heiman
  • Function : Author
Luis Herrera
  • Function : Author
Isobel Heyman
  • Function : Author
Anke Hinney
  • Function : Author
Matthew E Hirschtritt
  • Function : Author
Pieter J Hoekstra
  • Function : Author
Jae Hoon Sul
  • Function : Author
Hyun Ju Hong
  • Function : Author
David M Hougaard
  • Function : Author
Alden Y Huang
  • Function : Author
Laura Ibanez-Gomez
  • Function : Author
Franjo Ivankovic
  • Function : Author
Joseph Jankovic
  • Function : Author
Elinor K Karlsson
  • Function : Author
Jakko A Kaprio
  • Function : Author
Young Key Kim
  • Function : Author
Young-Shin Kim
  • Function : Author
Robert A King
  • Function : Author
James A Knowles
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Yun-Joo Koh
  • Function : Author
Sodham Kook
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Najah Khalifa
  • Function : Author
Anastasios Konstantinidis
  • Function : Author
Samuel Kuperman
  • Function : Author
Roger Kurlan
  • Function : Author
Gerd Kvale
  • Function : Author
James Leckman
  • Function : Author
Paul C Lee
  • Function : Author
Bennett Leventhal
  • Function : Author
Paul Lichtenstein
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Kerstin Lindbald-Toh
  • Function : Author
Thomas Lowe
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Andrea Ludolph
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Claudia Luhrs da Silva
  • Function : Author
Pétur Luðvigsson
  • Function : Author
Jurjen Luykx
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Gholson J Lyon
  • Function : Author
Behrang Mahjani
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Athanasios Maras
  • Function : Author
David Mataix-Cols
  • Function : Author
Manuel Mattheisen
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Carol A Mathews
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Irene A Malaty
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William M Mcmahon
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Andrew Mcquillin
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Sandra M Meier
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Tyne Miller-Fleming
  • Function : Author
Pablo Mir
  • Function : Author
Rainald Moessner
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Astrid Morer
  • Function : Author
Preben B Mortensen
  • Function : Author
Ole Mors
  • Function : Author
Poorva Mudgal
  • Function : Author
Kirsten R Muller-Vahl
  • Function : Author
Alexander Munchau
  • Function : Author
Peter Nagy
  • Function : Author
Allan Naarden
  • Function : Author
Benjamin M Neale
  • Function : Author
Muhammad S Nawaz
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Judith Becker Nissen
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Ashley E Nordsletten
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Michael S Okun
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Roel Ophoff
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Lisa Osiecki
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Aarno Palotie
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Teemu P Palviainen
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Carlos N Pato Michele T. Pato
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Christopher Pittenger
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Kerstin J Plessen
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Yehuda Pollak
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Danielle Posthuma
  • Function : Author
Eliana Ramos
  • Function : Author
Jennifer Reichert
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Renata Rizzo
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Mary M Robertson
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Veit Roessner
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Joshua L Roffman
  • Function : Author
Guy Rouleau
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Christian Rück
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Evald Sæmundsen
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Jack Samuels
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Sven Sandin
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Paul Sandor
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Monika Schlögelhofer
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Jeremiah M Scharf
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Eun-Young Shin
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Harvey S Singer
  • Function : Author
Jan Smit
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Jordan W Smoller
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Matthew State
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Stian Solem
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Dong-Ho Song
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Jungeun Song
  • Function : Author
Mara Stamenkovic
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Hreinn Stefansson
  • Function : Author
Kári Stefansson
  • Function : Author
Nora Strom
  • Function : Author
Manfred Stuhrmann
  • Function : Author
Jin Szatkiewicz
  • Function : Author
Urszula Szymanska
  • Function : Author
Zsanett Tarnok
  • Function : Author
Jay A Tischfield
  • Function : Author
Fotis Tsetsos
  • Function : Author
Ólafur Thorarensen
  • Function : Author
Jennifer Tubing
  • Function : Author
Frank Visscher
  • Function : Author
Michael Wagner
  • Function : Author
Sina Wanderer
  • Function : Author
Sheng Wang
  • Function : Author
Thomas Werge
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Jeremy A Willsey
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Tomasz Wolancyk
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Douglas W Woods
  • Function : Author
Martin Woods
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Yulia Worbe
  • Function : Author
Yves Dion
  • Function : Author
Dongmei Yu
  • Function : Author
Ivette Zelaya
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Samuel H Zinner
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Alan Apter
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Juliane Ball
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Benjamin Bodmer
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Emese Bognar
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Judith Buse
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Marta Correa Vela
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Carolin Fremer
  • Function : Author
Blanca Garcia-Delgar
  • Function : Author
Mariangela Gulisano
  • Function : Author
Annelieke Hagen
  • Function : Author
Julie Hagstrøm
  • Function : Author
Marcos Madruga-Garrido
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Peter Nagy
  • Function : Author
Alessandra Pellico
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Daphna Ruhrman
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Jaana Schnell
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Paola Rosaria Silvestri
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Liselotte Skov
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Tamar Steinberg
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Friederike Tagwerker Gloor
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Victoria L Turner
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Elif Weidinger
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Noa Benaroya-Milshtein
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Francesco Cardona
  • Function : Author
Andrea Dietrich
  • Function : Author
Marianthi Georgitsi
  • Function : Author
Tammy Hedderly
  • Function : Author
Isobel Heyman
  • Function : Author
Pieter J Hoekstra
  • Function : Author
Chaim Huyser
  • Function : Author
Davide Martino
  • Function : Author
Pablo Mir
  • Function : Author
Astrid Morer
  • Function : Author
Kirsten R Muller-Vahl
  • Function : Author
Peristera Paschou
  • Function : Author
Kerstin J Plessen
  • Function : Author
Cesare Porcelli
  • Function : Author
Renata Rizzo
  • Function : Author
Veit Roessner
  • Function : Author
Anette Schrag
  • Function : Author
Zsanett Tarnok
  • Function : Author
Andrea Dietrich
  • Function : Author
John Alexander
  • Function : Author
Tamas Aranyi
  • Function : Author
Wim R Buisman
  • Function : Author
Jan K Buitelaar
  • Function : Author
Nicole Driessen
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Petros Drineas
  • Function : Author
Siyan Fan
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Natalie J Forde
  • Function : Author
Sarah Gerasch
  • Function : Author
Odile A van den Heuvel
  • Function : Author
Cathrine Jespersgaard
  • Function : Author
Ahmad S Kanaan
  • Function : Author
Harald E Möller
  • Function : Author
Muhammad S Nawaz
  • Function : Author
Ester Nespoli
  • Function : Author
Luca Pagliaroli
  • Function : Author
Geert Poelmans
  • Function : Author
Petra J W Pouwels
  • Function : Author
Francesca Rizzo
  • Function : Author
Dick J Veltman
  • Function : Author
Ysbrand D van der Werf
  • Function : Author
Joanna Widomska
  • Function : Author
Nuno R Zilhäo
  • Function : Author
Csaba Barta
  • Function : Author
Dorret I Boomsma
  • Function : Author
Danielle C Cath
  • Function : Author
Marianthi Georgitsi
  • Function : Author
Jeffrey Glennon
  • Function : Author
Bastian Hengerer
  • Function : Author
Pieter J Hoekstra
  • Function : Author
Kirsten R Muller-Vahl
  • Function : Author
Peristera Paschou
  • Function : Author
Hreinn Stefansson
  • Function : Author
Zeynep Tumer
  • Function : Author
Carol A Mathews
Jeremiah M Scharf
  • Function : Author
Pieter J Hoekstra
  • Function : Author
Lea K Davis
  • Function : Author
Peristera Paschou
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Abstract

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.
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hal-04529833 , version 1 (02-04-2024)

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Pritesh Jain, Tyne Miller-Fleming, Apostolia Topaloudi, Dongmei Yu, Petros Drineas, et al.. Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome. Translational Psychiatry, 2023, 13, ⟨10.1038/s41398-023-02341-5⟩. ⟨hal-04529833⟩
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