Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
23 02 2023
23 02 2023
Historique:
received:
05
09
2022
accepted:
27
01
2023
revised:
23
01
2023
entrez:
23
2
2023
pubmed:
24
2
2023
medline:
3
3
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36823209
doi: 10.1038/s41398-023-02341-5
pii: 10.1038/s41398-023-02341-5
pmc: PMC9950421
doi:
Types de publication
Meta-Analysis
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
69Subventions
Organisme : NINDS NIH HHS
ID : R01 NS102371
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH124679
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG038072
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH126213
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS105746
Pays : United States
Investigateurs
Thomas D Als
(TD)
Harald Aschauer
(H)
Gil Atzmon
(G)
Matie Bækvad-Hansen
(M)
Csaba Barta
(C)
Cathy L Barr
(CL)
Nir Barzilai
(N)
James R Batterson
(JR)
Robert Batterson
(R)
Fortu Benarroch
(F)
Cheston Berlin
(C)
Julia Boberg
(J)
Benjamin Bodmer
(B)
Julia Bohnenpoll
(J)
Anders D Børglum
(AD)
Lawrence W Brown
(LW)
Ruth Bruun
(R)
Cathy L Budman
(CL)
Randy L Buckner
(RL)
Joseph D Buxbaum
(JD)
Jonas Bybjerg-Grauholm
(J)
Danielle C Cath
(DC)
Keun-Ah Cheon
(KA)
Sylvain Chouinard
(S)
Barbara J Coffey
(BJ)
Giovanni Coppola
(G)
James J Crowley
(JJ)
Niklas Dahl
(N)
Lea K Davis
(LK)
Sabrina M Darrow
(SM)
Mark J Daly
(MJ)
Christel Depienne
(C)
Silvia De Rubeis
(S)
Andrea Dietrich
(A)
Yves Dion
(Y)
Diana R Djurfeldt
(DR)
Laura Domenech-Salgado
(L)
Valsamma Eapen
(V)
Lonneke Elzerman
(L)
Thomas V Fernandez
(TV)
Nelson B Freimer Carolin Fremer
(NB)
Blanca Garcia-Delgar
(B)
Marcos Garrido
(M)
Donald L Gilbert
(DL)
Paola Giusti-Rodriguez
(P)
Marco Grados
(M)
Erica Greenberg
(E)
Jakob Grove
(J)
Dorothy E Grice
(DE)
Julie Hagstrom
(J)
Matt Halvorsen
(M)
Andreas Hartmann
(A)
Bjarne Hansen
(B)
Jan Haavik
(J)
Johannes Hebebrand
(J)
Gary A Heiman
(GA)
Luis Herrera
(L)
Isobel Heyman
(I)
Anke Hinney
(A)
Matthew E Hirschtritt
(ME)
Pieter J Hoekstra
(PJ)
Jae Hoon Sul
(JH)
Hyun Ju Hong
(HJ)
David M Hougaard
(DM)
Alden Y Huang
(AY)
Laura Ibanez-Gomez
(L)
Franjo Ivankovic
(F)
Joseph Jankovic
(J)
Elinor K Karlsson
(EK)
Jakko A Kaprio
(JA)
Young Key Kim
(YK)
Young-Shin Kim
(YS)
Robert A King
(RA)
James A Knowles
(JA)
Yun-Joo Koh
(YJ)
Sodham Kook
(S)
Najah Khalifa
(N)
Anastasios Konstantinidis
(A)
Samuel Kuperman
(S)
Roger Kurlan
(R)
Gerd Kvale
(G)
James Leckman
(J)
Paul C Lee
(PC)
Bennett Leventhal
(B)
Paul Lichtenstein
(P)
Kerstin Lindbald-Toh
(K)
Thomas Lowe
(T)
Andrea Ludolph
(A)
Claudia Luhrs da Silva
(CL)
Pétur Luðvigsson
(P)
Jurjen Luykx
(J)
Gholson J Lyon
(GJ)
Behrang Mahjani
(B)
Athanasios Maras
(A)
David Mataix-Cols
(D)
Manuel Mattheisen
(M)
Carol A Mathews
(CA)
Irene A Malaty
(IA)
William M McMahon
(WM)
Andrew McQuillin
(A)
Sandra M Meier
(SM)
Tyne Miller-Fleming
(T)
Pablo Mir
(P)
Rainald Moessner
(R)
Astrid Morer
(A)
Preben B Mortensen
(PB)
Ole Mors
(O)
Poorva Mudgal
(P)
Kirsten R Muller-Vahl
(KR)
Alexander Munchau
(A)
Peter Nagy
(P)
Allan Naarden
(A)
Benjamin M Neale
(BM)
Muhammad S Nawaz
(MS)
Judith Becker Nissen
(JB)
Markus M Nöthen Merete Nordentoft
(MM)
Ashley E Nordsletten
(AE)
Michael S Okun
(MS)
Roel Ophoff
(R)
Lisa Osiecki
(L)
Aarno Palotie
(A)
Teemu P Palviainen
(TP)
Peristera Paschou
(P)
Carlos N Pato Michele T Pato
(CN)
Christopher Pittenger
(C)
Kerstin J Plessen
(KJ)
Yehuda Pollak
(Y)
Danielle Posthuma
(D)
Eliana Ramos
(E)
Jennifer Reichert
(J)
Renata Rizzo
(R)
Mary M Robertson
(MM)
Veit Roessner
(V)
Joshua L Roffman
(JL)
Guy Rouleau
(G)
Christian Rück
(C)
Evald Sæmundsen
(E)
Jack Samuels
(J)
Sven Sandin
(S)
Paul Sandor
(P)
Monika Schlögelhofer
(M)
Jeremiah M Scharf
(JM)
Eun-Young Shin
(EY)
Harvey S Singer
(HS)
Jan Smit
(J)
Jordan W Smoller
(JW)
Matthew State
(M)
Stian Solem
(S)
Dong-Ho Song
(DH)
Jungeun Song
(J)
Mara Stamenkovic
(M)
Hreinn Stefansson
(H)
Kári Stefansson
(K)
Nora Strom
(N)
Manfred Stuhrmann
(M)
Jin Szatkiewicz
(J)
Urszula Szymanska
(U)
Zsanett Tarnok
(Z)
Jay A Tischfield
(JA)
Fotis Tsetsos
(F)
Ólafur Thorarensen
(Ó)
Jennifer Tubing
(J)
Frank Visscher
(F)
Michael Wagner
(M)
Sina Wanderer
(S)
Sheng Wang
(S)
Thomas Werge
(T)
Jeremy A Willsey
(JA)
Tomasz Wolancyk
(T)
Douglas W Woods
(DW)
Martin Woods
(M)
Yulia Worbe
(Y)
Yves Dion
(Y)
Dongmei Yu
(D)
Ivette Zelaya
(I)
Samuel H Zinner
(SH)
Alan Apter
(A)
Juliane Ball
(J)
Benjamin Bodmer
(B)
Emese Bognar
(E)
Judith Buse
(J)
Marta Correa Vela
(MC)
Carolin Fremer
(C)
Blanca Garcia-Delgar
(B)
Mariangela Gulisano
(M)
Annelieke Hagen
(A)
Julie Hagstrøm
(J)
Marcos Madruga-Garrido
(M)
Peter Nagy
(P)
Alessandra Pellico
(A)
Daphna Ruhrman
(D)
Jaana Schnell
(J)
Paola Rosaria Silvestri
(PR)
Liselotte Skov
(L)
Tamar Steinberg
(T)
Friederike Tagwerker Gloor
(FT)
Victoria L Turner
(VL)
Elif Weidinger
(E)
Noa Benaroya-Milshtein
(N)
Francesco Cardona
(F)
Andrea Dietrich
(A)
Marianthi Georgitsi
(M)
Tammy Hedderly
(T)
Isobel Heyman
(I)
Pieter J Hoekstra
(PJ)
Chaim Huyser
(C)
Davide Martino
(D)
Pablo Mir
(P)
Astrid Morer
(A)
Kirsten R Muller-Vahl
(KR)
Peristera Paschou
(P)
Kerstin J Plessen
(KJ)
Cesare Porcelli
(C)
Renata Rizzo
(R)
Veit Roessner
(V)
Anette Schrag
(A)
Zsanett Tarnok
(Z)
John Alexander
(J)
Tamas Aranyi
(T)
Wim R Buisman
(WR)
Jan K Buitelaar
(JK)
Nicole Driessen
(N)
Petros Drineas
(P)
Siyan Fan
(S)
Natalie J Forde
(NJ)
Sarah Gerasch
(S)
Odile A van den Heuvel
(OA)
Cathrine Jespersgaard
(C)
Ahmad S Kanaan
(AS)
Harald E Möller
(HE)
Muhammad S Nawaz
(MS)
Ester Nespoli
(E)
Luca Pagliaroli
(L)
Geert Poelmans
(G)
Petra J W Pouwels
(PJW)
Francesca Rizzo
(F)
Dick J Veltman
(DJ)
Ysbrand D van der Werf
(YD)
Joanna Widomska
(J)
Nuno R Zilhäo
(NR)
Csaba Barta
(C)
Dorret I Boomsma
(DI)
Danielle C Cath
(DC)
Marianthi Georgitsi
(M)
Jeffrey Glennon
(J)
Bastian Hengerer
(B)
Pieter J Hoekstra
(PJ)
Kirsten R Muller-Vahl
(KR)
Peristera Paschou
(P)
Hreinn Stefansson
(H)
Zeynep Tumer
(Z)
Informations de copyright
© 2023. The Author(s).
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