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Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome.
Jain, Pritesh; Miller-Fleming, Tyne; Topaloudi, Apostolia; Yu, Dongmei; Drineas, Petros; Georgitsi, Marianthi; Yang, Zhiyu; Rizzo, Renata; Müller-Vahl, Kirsten R; Tumer, Zeynep; Mol Debes, Nanette; Hartmann, Andreas; Depienne, Christel; Worbe, Yulia; Mir, Pablo; Cath, Danielle C; Boomsma, Dorret I; Roessner, Veit; Wolanczyk, Tomasz; Janik, Piotr; Szejko, Natalia; Zekanowski, Cezary; Barta, Csaba; Nemoda, Zsofia; Tarnok, Zsanett; Buxbaum, Joseph D; Grice, Dorothy; Glennon, Jeffrey; Stefansson, Hreinn; Hengerer, Bastian; Benaroya-Milshtein, Noa; Cardona, Francesco; Hedderly, Tammy; Heyman, Isobel; Huyser, Chaim; Morer, Astrid; Mueller, Norbert; Munchau, Alexander; Plessen, Kerstin J; Porcelli, Cesare; Walitza, Susanne; Schrag, Anette; Martino, Davide; Dietrich, Andrea; Mathews, Carol A; Scharf, Jeremiah M; Hoekstra, Pieter J; Davis, Lea K; Paschou, Peristera.
Afiliación
  • Jain P; Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.
  • Miller-Fleming T; Division of Genetic Medicine, Department of Medicine Vanderbilt University Medical Center Nashville, Nashville, TN, USA.
  • Topaloudi A; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Yu D; Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.
  • Drineas P; Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
  • Georgitsi M; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Yang Z; Department of Computer Science, Purdue University, West Lafayette, IN, USA.
  • Rizzo R; Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece.
  • Müller-Vahl KR; 1st Laboratory of Medical Biology-Genetics, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
  • Tumer Z; Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.
  • Mol Debes N; Child and Adolescent Neurology and Psychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
  • Hartmann A; Department of Psychiatry, Social psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.
  • Depienne C; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Worbe Y; Department of Clinical Genetics, Kennedy Center, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • Mir P; Department of Pediatrics, Herlev University Hospital, Herlev, Denmark.
  • Cath DC; Department of Neurology, Hôpital de la Pitié-Salpêtrière, Paris, France.
  • Boomsma DI; Institute for Human Genetics, University Hospital Essen, Essen, Germany.
  • Roessner V; Assistance Publique Hôpitaux de Paris, Sorbonne University, Faculty of Medicine Hopital Saint Antoine, Paris, France.
  • Wolanczyk T; French Reference Centre for Gilles de la Tourette Syndrome, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
  • Janik P; Unidad de Trastornos del Movimiento. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
  • Szejko N; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
  • Zekanowski C; Department of Clinical and health Psychology, Utrecht University, Utrecht, Netherlands.
  • Barta C; Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
  • Nemoda Z; EMGO+Institute for Health and Care Research, VU University Medical Centre, Amsterdam, Netherlands.
  • Tarnok Z; Department of Child and Adolescent Psychiatry, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany.
  • Buxbaum JD; Department of Child Psychiatry, Medical University of Warsaw, Warsaw, Poland.
  • Grice D; Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
  • Glennon J; Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
  • Stefansson H; Department of Bioethics, Medical University of Warsaw, Warsaw, Poland.
  • Hengerer B; Department of Neurogenetics and Functional Genomics, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
  • Benaroya-Milshtein N; Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary.
  • Cardona F; Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary.
  • Hedderly T; Vadaskert Clinic for Child and Adolescent Psychiatry, Budapest, Hungary.
  • Heyman I; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Huyser C; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Morer A; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Mueller N; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Munchau A; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Plessen KJ; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Porcelli C; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Walitza S; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Schrag A; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Martino D; Division of Tics, OCD, and Related Disorders, Icahn School of Medicine at Mount Sinai, New York, USA.
  • Dietrich A; Boehringer Ingelheim Pharma GmbH & Co. KG, CNS Research, Boehringer, Germany.
  • Mathews CA; Department of Human Neurosciences, University La Sapienza of Rome, Rome, Italy.
  • Scharf JM; Evelina London Children's Hospital GSTT, Kings Health Partners AHSC, London, UK.
  • Hoekstra PJ; Psychological Medicine, Great Ormond Street Hospital NHS Foundation Trust, Great Ormond Street, London, UK.
  • Davis LK; Levvel, Academic Center for Child and Adolescent Psychiatry, Amsterdam, The Netherlands.
  • Paschou P; Amsterdam UMC, Department of Child and Adolescent Psychiatry, Amsterdam, The Netherlands.
Transl Psychiatry ; 13(1): 69, 2023 02 23.
Article en En | MEDLINE | ID: mdl-36823209
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Trastorno por Déficit de Atención con Hiperactividad / Síndrome de Tourette / Diabetes Mellitus Tipo 2 / Trastorno del Espectro Autista Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Female / Humans / Male Idioma: En Revista: Transl Psychiatry Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Trastorno por Déficit de Atención con Hiperactividad / Síndrome de Tourette / Diabetes Mellitus Tipo 2 / Trastorno del Espectro Autista Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Female / Humans / Male Idioma: En Revista: Transl Psychiatry Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos