TY - JOUR
T1 - Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome
AU - Jain, Pritesh
AU - Miller-Fleming, Tyne
AU - Topaloudi, Apostolia
AU - Yu, Dongmei
AU - Drineas, Petros
AU - Georgitsi, Marianthi
AU - Yang, Zhiyu
AU - Rizzo, Renata
AU - Müller-Vahl, Kirsten R.
AU - Tumer, Zeynep
AU - Mol debes, Nanette
AU - Hartmann, Andreas
AU - Depienne, Christel
AU - Worbe, Yulia
AU - Mir, Pablo
AU - Cath, Danielle C.
AU - Boomsma, Dorret I.
AU - Roessner, Veit
AU - Wolanczyk, Tomasz
AU - Janik, Piotr
AU - Szejko, Natalia
AU - Zekanowski, Cezary
AU - Barta, Csaba
AU - Nemoda, Zsofia
AU - Tarnok, Zsanett
AU - Buxbaum, Joseph D.
AU - Grice, Dorothy
AU - Glennon, Jeffrey
AU - Stefansson, Hreinn
AU - Hengerer, Bastian
AU - Benaroya-Milshtein, Noa
AU - Cardona, Francesco
AU - Hedderly, Tammy
AU - Heyman, Isobel
AU - Huyser, Chaim
AU - Morer, Astrid
AU - Mueller, Norbert
AU - Munchau, Alexander
AU - Plessen, Kerstin J.
AU - Porcelli, Cesare
AU - Walitza, Susanne
AU - Schrag, Anette
AU - Martino, Davide
AU - Als, Thomas D.
AU - Aschauer, Harald
AU - Atzmon, Gil
AU - Bækvad-Hansen, Matie
AU - Barta, Csaba
AU - Barr, Cathy L.
AU - Barzilai, Nir
AU - Batterson, James R.
AU - Batterson, Robert
AU - Benarroch, Fortu
AU - Berlin, Cheston
AU - Boberg, Julia
AU - Bodmer, Benjamin
AU - Bohnenpoll, Julia
AU - Børglum, Anders D.
AU - Brown, Lawrence W.
AU - Bruun, Ruth
AU - Budman, Cathy L.
AU - Buckner, Randy L.
AU - Buxbaum, Joseph D.
AU - Bybjerg-Grauholm, Jonas
AU - Cath, Danielle C.
AU - Cheon, Keun-ah
AU - Chouinard, Sylvain
AU - Coffey, Barbara J.
AU - Coppola, Giovanni
AU - Crowley, James J.
AU - Dahl, Niklas
AU - Davis, Lea K.
AU - Darrow, Sabrina M.
AU - Daly, Mark J.
AU - Depienne, Christel
AU - De rubeis, Silvia
AU - Dietrich, Andrea
AU - Dion, Yves
AU - Djurfeldt, Diana R.
AU - Domenech-Salgado, Laura
AU - Eapen, Valsamma
AU - Elzerman, Lonneke
AU - Fernandez, Thomas V.
AU - Freimer carolin fremer, Nelson B.
AU - Garcia-Delgar, Blanca
AU - Garrido, Marcos
AU - Gilbert, Donald L.
AU - Giusti-Rodriguez, Paola
AU - Grados, Marco
AU - Greenberg, Erica
AU - Grove, Jakob
AU - Grice, Dorothy E.
AU - Hagstrom, Julie
AU - Halvorsen, Matt
AU - Hartmann, Andreas
AU - Hansen, Bjarne
AU - Haavik, Jan
AU - Hebebrand, Johannes
AU - Heiman, Gary A.
AU - Herrera, Luis
AU - Heyman, Isobel
AU - Hinney, Anke
AU - Hirschtritt, Matthew E.
AU - Hoekstra, Pieter J.
AU - Sul, Jae Hoon
AU - Hong, Hyun Ju
AU - Hougaard, David M.
AU - Huang, Alden Y.
AU - Ibanez-Gomez, Laura
AU - Ivankovic, Franjo
AU - Jankovic, Joseph
AU - Karlsson, Elinor K.
AU - Kaprio, Jakko A.
AU - Kim, Young Key
AU - Kim, Young-shin
AU - King, Robert A.
AU - Knowles, James A.
AU - Koh, Yun-joo
AU - Kook, Sodham
AU - Khalifa, Najah
AU - Konstantinidis, Anastasios
AU - Kuperman, Samuel
AU - Kurlan, Roger
AU - Kvale, Gerd
AU - Leckman, James
AU - Lee, Paul C.
AU - Leventhal, Bennett
AU - Lichtenstein, Paul
AU - Lindbald-Toh, Kerstin
AU - Lowe, Thomas
AU - Ludolph, Andrea
AU - Da silva, Claudia Luhrs
AU - Luðvigsson, Pétur
AU - Luykx, Jurjen
AU - Lyon, Gholson J.
AU - Mahjani, Behrang
AU - Maras, Athanasios
AU - Mataix-Cols, David
AU - Mattheisen, Manuel
AU - Mathews, Carol A.
AU - Malaty, Irene A.
AU - Mcmahon, William M.
AU - Mcquillin, Andrew
AU - Meier, Sandra M.
AU - Miller-Fleming, Tyne
AU - Mir, Pablo
AU - Moessner, Rainald
AU - Morer, Astrid
AU - Mortensen, Preben B.
AU - Mors, Ole
AU - Mudgal, Poorva
AU - Muller-Vahl, Kirsten R.
AU - Munchau, Alexander
AU - Nagy, Peter
AU - Naarden, Allan
AU - Neale, Benjamin M.
AU - Nawaz, Muhammad S.
AU - Nissen, Judith Becker
AU - Nöthen merete nordentoft, Markus M.
AU - Nordsletten, Ashley E.
AU - Okun, Michael S.
AU - Ophoff, Roel
AU - Osiecki, Lisa
AU - Palotie, Aarno
AU - Palviainen, Teemu P.
AU - Paschou, Peristera
AU - Pato michele t. pato, Carlos N.
AU - Pittenger, Christopher
AU - Plessen, Kerstin J.
AU - Pollak, Yehuda
AU - Posthuma, Danielle
AU - Ramos, Eliana
AU - Reichert, Jennifer
AU - Rizzo, Renata
AU - Robertson, Mary M.
AU - Roessner, Veit
AU - Roffman, Joshua L.
AU - Rouleau, Guy
AU - Rück, Christian
AU - Sæmundsen, Evald
AU - Samuels, Jack
AU - Sandin, Sven
AU - Sandor, Paul
AU - Schlögelhofer, Monika
AU - Scharf, Jeremiah M.
AU - Shin, Eun-young
AU - Singer, Harvey S.
AU - Smit, Jan
AU - Smoller, Jordan W.
AU - State, Matthew
AU - Solem, Stian
AU - Song, Dong-ho
AU - Song, Jungeun
AU - Stamenkovic, Mara
AU - Stefansson, Hreinn
AU - Stefansson, Kári
AU - Strom, Nora
AU - Stuhrmann, Manfred
AU - Szatkiewicz, Jin
AU - Szymanska, Urszula
AU - Tarnok, Zsanett
AU - Tischfield, Jay A.
AU - Tsetsos, Fotis
AU - Thorarensen, Ólafur
AU - Tubing, Jennifer
AU - Visscher, Frank
AU - Wagner, Michael
AU - Wanderer, Sina
AU - Wang, Sheng
AU - Werge, Thomas
AU - Willsey, Jeremy A.
AU - Wolancyk, Tomasz
AU - Woods, Douglas W.
AU - Woods, Martin
AU - Worbe, Yulia
AU - Dion, Yves
AU - Yu, Dongmei
AU - Zelaya, Ivette
AU - Zinner, Samuel H.
AU - Apter, Alan
AU - Ball, Juliane
AU - Bodmer, Benjamin
AU - Bognar, Emese
AU - Buse, Judith
AU - Vela, Marta Correa
AU - Fremer, Carolin
AU - Garcia-Delgar, Blanca
AU - Gulisano, Mariangela
AU - Hagen, Annelieke
AU - Hagstrøm, Julie
AU - Madruga-Garrido, Marcos
AU - Nagy, Peter
AU - Pellico, Alessandra
AU - Ruhrman, Daphna
AU - Schnell, Jaana
AU - Silvestri, Paola Rosaria
AU - Skov, Liselotte
AU - Steinberg, Tamar
AU - Gloor, Friederike Tagwerker
AU - Turner, Victoria L.
AU - Weidinger, Elif
AU - Benaroya-Milshtein, Noa
AU - Cardona, Francesco
AU - Dietrich, Andrea
AU - Georgitsi, Marianthi
AU - Hedderly, Tammy
AU - Heyman, Isobel
AU - Hoekstra, Pieter J.
AU - Huyser, Chaim
AU - Martino, Davide
AU - Mir, Pablo
AU - Morer, Astrid
AU - Muller-Vahl, Kirsten R.
AU - Paschou, Peristera
AU - Plessen, Kerstin J.
AU - Porcelli, Cesare
AU - Rizzo, Renata
AU - Roessner, Veit
AU - Schrag, Anette
AU - Tarnok, Zsanett
AU - Dietrich, Andrea
AU - Alexander, John
AU - Aranyi, Tamas
AU - Buisman, Wim R.
AU - Buitelaar, Jan K.
AU - Driessen, Nicole
AU - Drineas, Petros
AU - Fan, Siyan
AU - Forde, Natalie J.
AU - Gerasch, Sarah
AU - Van den heuvel, Odile A.
AU - Jespersgaard, Cathrine
AU - Kanaan, Ahmad S.
AU - Möller, Harald E.
AU - Nawaz, Muhammad S.
AU - Nespoli, Ester
AU - Pagliaroli, Luca
AU - Poelmans, Geert
AU - Pouwels, Petra J. W.
AU - Rizzo, Francesca
AU - Veltman, Dick J.
AU - Van der werf, Ysbrand D.
AU - Widomska, Joanna
AU - Zilhäo, Nuno R.
AU - Barta, Csaba
AU - Boomsma, Dorret I.
AU - Cath, Danielle C.
AU - Georgitsi, Marianthi
AU - Glennon, Jeffrey
AU - Hengerer, Bastian
AU - Hoekstra, Pieter J.
AU - Muller-Vahl, Kirsten R.
AU - Paschou, Peristera
AU - Stefansson, Hreinn
AU - Tumer, Zeynep
AU - Mathews, Carol A.
AU - Scharf, Jeremiah M.
AU - Hoekstra, Pieter J.
AU - Davis, Lea K.
AU - Paschou, Peristera
AU - Psychiatric Genomics Consortium Tourette Syndrome Working Group
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1038/s41398-023-02341-5
DO - 10.1038/s41398-023-02341-5
M3 - Article
SN - 2158-3188
VL - 13
SP - 1
EP - 10
JO - Translational Psychiatry
JF - Translational Psychiatry
M1 - 69
ER -