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 phenot...
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-02-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02341-5 |
| _version_ | 1797863443409141760 |
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| author | 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 The Psychiatric Genomics Consortium Tourette Syndrome Working Group (PGC-TS) The EMTICS collaborative group Andrea Dietrich The TS-EUROTRAIN Network Carol A. Mathews Jeremiah M. Scharf Pieter J. Hoekstra Lea K. Davis Peristera Paschou |
| author_facet | 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 The Psychiatric Genomics Consortium Tourette Syndrome Working Group (PGC-TS) The EMTICS collaborative group Andrea Dietrich The TS-EUROTRAIN Network Carol A. Mathews Jeremiah M. Scharf Pieter J. Hoekstra Lea K. Davis Peristera Paschou |
| author_sort | Pritesh Jain |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T22:35:40Z |
| format | Article |
| id | doaj.art-0f10e24c351c4984a4de93efa5a3d079 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-09T22:35:40Z |
| publishDate | 2023-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-0f10e24c351c4984a4de93efa5a3d0792023-03-22T12:27:25ZengNature Publishing GroupTranslational Psychiatry2158-31882023-02-0113111010.1038/s41398-023-02341-5Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndromePritesh Jain0Tyne Miller-Fleming1Apostolia Topaloudi2Dongmei Yu3Petros Drineas4Marianthi Georgitsi5Zhiyu Yang6Renata Rizzo7Kirsten R. Müller-Vahl8Zeynep Tumer9Nanette Mol Debes10Andreas Hartmann11Christel Depienne12Yulia Worbe13Pablo Mir14Danielle C. Cath15Dorret I. Boomsma16Veit Roessner17Tomasz Wolanczyk18Piotr Janik19Natalia Szejko20Cezary Zekanowski21Csaba Barta22Zsofia Nemoda23Zsanett Tarnok24Joseph D. Buxbaum25Dorothy Grice26Jeffrey Glennon27Hreinn Stefansson28Bastian Hengerer29Noa Benaroya-Milshtein30Francesco Cardona31Tammy Hedderly32Isobel Heyman33Chaim Huyser34Astrid Morer35Norbert Mueller36Alexander Munchau37Kerstin J. Plessen38Cesare Porcelli39Susanne Walitza40Anette Schrag41Davide Martino42The Psychiatric Genomics Consortium Tourette Syndrome Working Group (PGC-TS)The EMTICS collaborative groupAndrea Dietrich43The TS-EUROTRAIN NetworkCarol A. Mathews44Jeremiah M. Scharf45Pieter J. Hoekstra46Lea K. Davis47Peristera Paschou48Department of Biological Sciences, Purdue UniversityDivision of Genetic Medicine, Department of Medicine Vanderbilt University Medical Center NashvilleDepartment of Biological Sciences, Purdue UniversityPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Department of Psychiatry, Massachusetts General HospitalDepartment of Computer Science, Purdue UniversityDepartment of Molecular Biology and Genetics, Democritus University of ThraceDepartment of Biological Sciences, Purdue UniversityChild and Adolescent Neurology and Psychiatry, Department of Clinical and Experimental Medicine, University of CataniaDepartment of Psychiatry, Social psychiatry and Psychotherapy, Hannover Medical SchoolDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Pediatrics, Herlev University HospitalDepartment of Neurology, Hôpital de la Pitié-SalpêtrièreInstitute for Human Genetics, University Hospital EssenAssistance Publique Hôpitaux de Paris, Sorbonne University, Faculty of Medicine Hopital Saint AntoineUnidad de Trastornos del Movimiento. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaDepartment of Clinical and health Psychology, Utrecht UniversityInstitute for Anatomy and Cell Biology, Ulm UniversityDepartment of Child and Adolescent Psychiatry, Medical Faculty Carl Gustav Carus, TU DresdenDepartment of Child Psychiatry, Medical University of WarsawDepartment of Neurology, Medical University of WarsawDepartment of Neurology, Medical University of WarsawDepartment of Neurogenetics and Functional Genomics, Mossakowski Medical Research Institute, Polish Academy of SciencesDepartment of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis UniversityDepartment of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis UniversityVadaskert Clinic for Child and Adolescent PsychiatryDepartment of Psychiatry, Icahn School of Medicine at Mount SinaiDepartment of Psychiatry, Icahn School of Medicine at Mount SinaiDepartment of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical CenterdeCODE Genetics/AmgenBoehringer Ingelheim Pharma GmbH & Co. KG, CNS ResearchChild and Adolescent Psychiatry Department, Schneider Children’s Medical Centre of Israel, Petah-Tikva. Affiliated to Sackler Faculty of Medicine, Tel Aviv UniversityDepartment of Human Neurosciences, University La Sapienza of RomeEvelina London Children’s Hospital GSTT, Kings Health Partners AHSCPsychological Medicine, Great Ormond Street Hospital NHS Foundation TrustLevvel, Academic Center for Child and Adolescent PsychiatryDepartment of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic UniversitarioDepartment of Psychiatry and Psychotherapy, University Hospital, LMU MunichInstitute of Systems Motor Science, University of LübeckChild and Adolescent Mental Health Centre, Mental Health Services, Capital Region of Denmark and University of CopenhagenASL BA, Maternal and Childood Department, Adolescence and Childhood Neuropsychiatry UnitDepartment of Child and Adolescent Psychiatry and Psychotherapy, University of ZurichDepartment of Clinical and Movement Neurosciences, UCL Institute of Neurology, University College LondonDepartment of Clinical Neurosciences, Cumming School of Medicine & Hotchkiss Brain Institute, University of CalgaryUniversity of Groningen, University Medical Center Groningen, Department of Child and Adolescent PsychiatryDepartment of Psychiatry and Genetics Institute, University of Florida College of MedicinePsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Department of Psychiatry, Massachusetts General HospitalUniversity of Groningen, University Medical Center Groningen, Department of Child and Adolescent PsychiatryDivision of Genetic Medicine, Department of Medicine Vanderbilt University Medical Center NashvilleDepartment of Biological Sciences, Purdue UniversityAbstract 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.https://doi.org/10.1038/s41398-023-02341-5 |
| spellingShingle | 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 The Psychiatric Genomics Consortium Tourette Syndrome Working Group (PGC-TS) The EMTICS collaborative group Andrea Dietrich The TS-EUROTRAIN Network Carol A. Mathews Jeremiah M. Scharf Pieter J. Hoekstra Lea K. Davis Peristera Paschou Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome Translational Psychiatry |
| title | Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome |
| title_full | Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome |
| title_fullStr | Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome |
| title_full_unstemmed | Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome |
| title_short | Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome |
| title_sort | polygenic risk score based phenome wide association study identifies novel associations for tourette syndrome |
| url | https://doi.org/10.1038/s41398-023-02341-5 |
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