Translational Psychiatry (Feb 2023)
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,
- 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
Affiliations
- Pritesh Jain
- Department of Biological Sciences, Purdue University
- Tyne Miller-Fleming
- Division of Genetic Medicine, Department of Medicine Vanderbilt University Medical Center Nashville
- Apostolia Topaloudi
- Department of Biological Sciences, Purdue University
- Dongmei Yu
- Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Department of Psychiatry, Massachusetts General Hospital
- Petros Drineas
- Department of Computer Science, Purdue University
- Marianthi Georgitsi
- Department of Molecular Biology and Genetics, Democritus University of Thrace
- Zhiyu Yang
- Department of Biological Sciences, Purdue University
- Renata Rizzo
- Child and Adolescent Neurology and Psychiatry, Department of Clinical and Experimental Medicine, University of Catania
- Kirsten R. Müller-Vahl
- Department of Psychiatry, Social psychiatry and Psychotherapy, Hannover Medical School
- Zeynep Tumer
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen
- Nanette Mol Debes
- Department of Pediatrics, Herlev University Hospital
- Andreas Hartmann
- Department of Neurology, Hôpital de la Pitié-Salpêtrière
- Christel Depienne
- Institute for Human Genetics, University Hospital Essen
- Yulia Worbe
- Assistance Publique Hôpitaux de Paris, Sorbonne University, Faculty of Medicine Hopital Saint Antoine
- Pablo Mir
- Unidad de Trastornos del Movimiento. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla
- Danielle C. Cath
- Department of Clinical and health Psychology, Utrecht University
- Dorret I. Boomsma
- Institute for Anatomy and Cell Biology, Ulm University
- Veit Roessner
- Department of Child and Adolescent Psychiatry, Medical Faculty Carl Gustav Carus, TU Dresden
- Tomasz Wolanczyk
- Department of Child Psychiatry, Medical University of Warsaw
- Piotr Janik
- Department of Neurology, Medical University of Warsaw
- Natalia Szejko
- Department of Neurology, Medical University of Warsaw
- Cezary Zekanowski
- Department of Neurogenetics and Functional Genomics, Mossakowski Medical Research Institute, Polish Academy of Sciences
- Csaba Barta
- Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University
- Zsofia Nemoda
- Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University
- Zsanett Tarnok
- Vadaskert Clinic for Child and Adolescent Psychiatry
- Joseph D. Buxbaum
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai
- Dorothy Grice
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai
- Jeffrey Glennon
- Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center
- Hreinn Stefansson
- deCODE Genetics/Amgen
- Bastian Hengerer
- Boehringer Ingelheim Pharma GmbH & Co. KG, CNS Research
- Noa Benaroya-Milshtein
- Child and Adolescent Psychiatry Department, Schneider Children’s Medical Centre of Israel, Petah-Tikva. Affiliated to Sackler Faculty of Medicine, Tel Aviv University
- Francesco Cardona
- Department of Human Neurosciences, University La Sapienza of Rome
- Tammy Hedderly
- Evelina London Children’s Hospital GSTT, Kings Health Partners AHSC
- Isobel Heyman
- Psychological Medicine, Great Ormond Street Hospital NHS Foundation Trust
- Chaim Huyser
- Levvel, Academic Center for Child and Adolescent Psychiatry
- Astrid Morer
- Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic Universitario
- Norbert Mueller
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich
- Alexander Munchau
- Institute of Systems Motor Science, University of Lübeck
- Kerstin J. Plessen
- Child and Adolescent Mental Health Centre, Mental Health Services, Capital Region of Denmark and University of Copenhagen
- Cesare Porcelli
- ASL BA, Maternal and Childood Department, Adolescence and Childhood Neuropsychiatry Unit
- Susanne Walitza
- Department of Child and Adolescent Psychiatry and Psychotherapy, University of Zurich
- Anette Schrag
- Department of Clinical and Movement Neurosciences, UCL Institute of Neurology, University College London
- Davide Martino
- Department of Clinical Neurosciences, Cumming School of Medicine & Hotchkiss Brain Institute, University of Calgary
- The Psychiatric Genomics Consortium Tourette Syndrome Working Group (PGC-TS)
- The EMTICS collaborative group
- Andrea Dietrich
- University of Groningen, University Medical Center Groningen, Department of Child and Adolescent Psychiatry
- The TS-EUROTRAIN Network
- Carol A. Mathews
- Department of Psychiatry and Genetics Institute, University of Florida College of Medicine
- Jeremiah M. Scharf
- Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Department of Psychiatry, Massachusetts General Hospital
- Pieter J. Hoekstra
- University of Groningen, University Medical Center Groningen, Department of Child and Adolescent Psychiatry
- Lea K. Davis
- Division of Genetic Medicine, Department of Medicine Vanderbilt University Medical Center Nashville
- Peristera Paschou
- Department of Biological Sciences, Purdue University
- DOI
- https://doi.org/10.1038/s41398-023-02341-5
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 10
Abstract
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.
