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

Pritesh Jain; Tyne Miller-Fleming; Apostolia Topaloudi; Dongmei Yu; Petros Drineas; Marianthi Georgitsi; Zhiyu Yang; Renata Rizzo; Kirsten R. Müller-Vahl; Zeynep Tumer; Nanette Mol Debes; Andreas Hartmann; Christel Depienne; Yulia Worbe; Pablo Mir; Danielle C. Cath; Dorret I. Boomsma; Veit Roessner; Tomasz Wolanczyk; Piotr Janik; Natalia Szejko; Cezary Zekanowski; Csaba Barta; Zsofia Nemoda; 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; Andrea Dietrich; Carol A. Mathews; Jeremiah M. Scharf; Pieter J. Hoekstra; Lea K. Davis; Peristera Paschou; Psychiatric Genomics Consortium Tourette Syndrome Working Group (PGC-TS); EMTICS Collaborative Group; TS-EUROTRAIN Network

doi:10.1038/s41398-023-02341-5

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

Pritesh Jain, Tyne Miller-Fleming, Apostolia Topaloudi, Dongmei Yu, Petros Drineas, Marianthi Georgitsi, Zhiyu Yang, Renata Rizzo, Kirsten R. Müller-Vahl, Zeynep Tumer, Nanette Mol Debes, Andreas Hartmann, Christel Depienne, Yulia Worbe, Pablo Mir, Danielle C. Cath, Dorret I. Boomsma, Veit Roessner, Tomasz Wolanczyk, Piotr JanikNatalia Szejko, Cezary Zekanowski, Csaba Barta, Zsofia Nemoda, 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, Andrea Dietrich, Carol A. Mathews, Jeremiah M. Scharf, Pieter J. Hoekstra, Lea K. Davis, Peristera Paschou, Psychiatric Genomics Consortium Tourette Syndrome Working Group (PGC-TS), EMTICS Collaborative Group, TS-EUROTRAIN Network

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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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.

Originalsprog	Engelsk
Artikelnummer	69
Tidsskrift	Translational Psychiatry
Vol/bind	13
Antal sider	10
ISSN	2158-3188
DOI	https://doi.org/10.1038/s41398-023-02341-5
Status	Udgivet - 2023

Bibliografisk note

Publisher Copyright:
© 2023. The Author(s).

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10.1038/s41398-023-02341-5Licens: CC BY

FulltextForlagets udgivne version, 3,18 MBLicens: CC BY

Citationsformater

Jain, P., Miller-Fleming, T., Topaloudi, A., Yu, D., Drineas, P., Georgitsi, M., Yang, Z., Rizzo, R., Müller-Vahl, K. R., Tumer, Z., Mol Debes, N., Hartmann, A., Depienne, C., Worbe, Y., Mir, P., Cath, D. C., Boomsma, D. I., Roessner, V., Wolanczyk, T., ... TS-EUROTRAIN Network (2023). Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome. Translational Psychiatry, 13, Artikel 69. https://doi.org/10.1038/s41398-023-02341-5

Jain, P, Miller-Fleming, T, Topaloudi, A, Yu, D, Drineas, P, Georgitsi, M, Yang, Z, Rizzo, R, Müller-Vahl, KR, Tumer, Z, Mol Debes, N, Hartmann, A, Depienne, C, Worbe, Y, Mir, P, Cath, DC, Boomsma, DI, Roessner, V, Wolanczyk, T, Janik, P, Szejko, N, Zekanowski, C, Barta, C, Nemoda, Z, Tarnok, Z, Buxbaum, JD, Grice, D, Glennon, J, Stefansson, H, Hengerer, B, Benaroya-Milshtein, N, Cardona, F, Hedderly, T, Heyman, I, Huyser, C, Morer, A, Mueller, N, Munchau, A, Plessen, KJ, Porcelli, C, Walitza, S, Schrag, A, Martino, D, Dietrich, A, Mathews, CA, Scharf, JM, Hoekstra, PJ, Davis, LK, Paschou, P, Psychiatric Genomics Consortium Tourette Syndrome Working Group (PGC-TS), EMTICS Collaborative Group & TS-EUROTRAIN Network 2023, 'Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome', Translational Psychiatry, bind 13, 69. https://doi.org/10.1038/s41398-023-02341-5

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title = "Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome",

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.",

author = "Pritesh Jain and Tyne Miller-Fleming and Apostolia Topaloudi and Dongmei Yu and Petros Drineas and Marianthi Georgitsi and Zhiyu Yang and Renata Rizzo and M{\"u}ller-Vahl, {Kirsten R.} and Zeynep Tumer and {Mol Debes}, Nanette and Andreas Hartmann and Christel Depienne and Yulia Worbe and Pablo Mir and Cath, {Danielle C.} and Boomsma, {Dorret I.} and Veit Roessner and Tomasz Wolanczyk and Piotr Janik and Natalia Szejko and Cezary Zekanowski and Csaba Barta and Zsofia Nemoda and Zsanett Tarnok and Buxbaum, {Joseph D.} and Dorothy Grice and Jeffrey Glennon and Hreinn Stefansson and Bastian Hengerer and Noa Benaroya-Milshtein and Francesco Cardona and Tammy Hedderly and Isobel Heyman and Chaim Huyser and Astrid Morer and Norbert Mueller and Alexander Munchau and Plessen, {Kerstin J.} and Cesare Porcelli and Susanne Walitza and Anette Schrag and Davide Martino and Andrea Dietrich and Mathews, {Carol A.} and Scharf, {Jeremiah M.} and Hoekstra, {Pieter J.} and Davis, {Lea K.} and Peristera Paschou and {Psychiatric Genomics Consortium Tourette Syndrome Working Group (PGC-TS)} and {EMTICS Collaborative Group} and {TS-EUROTRAIN Network}",

note = "Publisher Copyright: {\textcopyright} 2023. The Author(s).",

year = "2023",

doi = "10.1038/s41398-023-02341-5",

language = "English",

volume = "13",

journal = "Translational Psychiatry",

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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 - Dietrich, Andrea

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 (PGC-TS)

AU - EMTICS Collaborative Group

AU - TS-EUROTRAIN Network

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 - Journal article

C2 - 36823209

AN - SCOPUS:85148805353

SN - 2158-3188

VL - 13

JO - Translational Psychiatry

JF - Translational Psychiatry

M1 - 69

ER -