Genomics yields biological and phenotypic insights into bipolar disorder
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články
Grantová podpora
001
World Health Organization - International
PubMed
39843750
DOI
10.1038/s41586-024-08468-9
PII: 10.1038/s41586-024-08468-9
Knihovny.cz E-zdroje
- MeSH
- Asijci genetika MeSH
- běloch MeSH
- běloši genetika MeSH
- bipolární porucha * genetika MeSH
- celogenomová asociační studie * MeSH
- černoši nebo Afroameričané genetika MeSH
- fenotyp * MeSH
- GABAergní neurony metabolismus MeSH
- genetická predispozice k nemoci MeSH
- genomika * MeSH
- Hispánci a Latinoameričané genetika MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Bipolar disorder is a leading contributor to the global burden of disease1. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown2. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings3, and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder4, highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder.
Academic Psychiatry Newcastle University Newcastle upon Tyne UK
Analytic and Translational Genetics Unit Massachusetts General Hospital Boston MA USA
Banner University Medical Center Phoenix AZ USA
Biochemistry and Molecular Biology Indiana University School of Medicine Indianapolis IN USA
Bioinformatics Research Centre Aarhus University Aarhus Denmark
Brain and Mind Centre The University of Sydney Sydney New South Wales Australia
Carl T Hayden Veterans Affairs Medical Center Phoenix AZ USA
Center for Disease Neurogenomics Icahn School of Medicine at Mount Sinai New York NY USA
Center for Genomics and Personalized Medicine CGPM Aarhus Denmark
Center for GeoGenetics GLOBE Institute University of Copenhagen Copenhagen Denmark
Center for Molecular Medicine Karolinska University Hospital Stockholm Sweden
Center for Molecular Medicine Stockholm Sweden
Center for Precision Psychiatry University of Oslo Oslo Norway
Centre for Human Genetics University of Marburg Marburg Germany
Centre for Integrated Register based Research Aarhus University Aarhus Denmark
Centre for Psychiatry Research SLSO Region Stockholm Stockholm Sweden
Centro de Biología Molecular Severo Ochoa Universidad Autónoma de Madrid and CSIC Madrid Spain
Clinic for Psychiatry and Psychotherapy University Hospital Cologne Cologne Germany
Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy
Department of Biomedical Sciences University of Cagliari Cagliari Italy
Department of Biomedicine and the iSEQ Center Aarhus University Aarhus Denmark
Department of Biomedicine Human Genetics Aarhus University Aarhus Denmark
Department of Biomedicine University of Basel Basel Switzerland
Department of Clinical Medicine University of Copenhagen Copenhagen Denmark
Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden
Department of Clinical Science University of Bergen Bergen Norway
Department of Clinical Sciences Psychiatry Umeå University Medical Faculty Umeå Sweden
Department of Environmental Epidemiology Nofer Institute of Occupational Medicine Lodz Poland
Department of Genetics and Bioinformatics Norwegian Institute of Public Health Oslo Norway
Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York NY USA
Department of Genetics University of North Carolina at Chapel Hill Chapel Hill NC USA
Department of Human Genetics University of Chicago Chicago IL USA
Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden
Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
Department of Medical Genetics Oslo University Hospital Ullevål Oslo Norway
Department of Medicine and Surgery Kore University of Enna Enna Italy
Department of Mental Disorders Norwegian Institute of Public Health Oslo Norway
Department of Neurology Oslo University Hospital Oslo Norway
Department of Neuropsychiatry Seoul National University Bundang Hospital Seongnam Republic of Korea
Department of Neuropsychiatry Seoul National University College of Medicine Seoul Republic of Korea
Department of Neuroscience Istituto Di Ricerche Farmacologiche Mario Negri IRCCS Milano Italy
Department of Neuroscience SUNY Upstate Medical University Syracuse NY USA
Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden
Department of Psychiatric Genetics Poznan University of Medical Sciences Poznan Poland
Department of Psychiatry Amsterdam University Medical Center Amsterdam The Netherlands
Department of Psychiatry and Behavioral Neuroscience University of Chicago Chicago IL USA
Department of Psychiatry and Behavioral Sciences Emory University School of Medicine Atlanta GA USA
Department of Psychiatry and Behavioral Sciences SUNY Upstate Medical University Syracuse NY USA
Department of Psychiatry and Forensic Medicine Universitat Autònoma de Barcelona Barcelona Spain
Department of Psychiatry and Neurobehavioral Science University College Cork Cork Ireland
Department of Psychiatry and Psychology Mayo Clinic Rochester MN USA
Department of Psychiatry and Psychotherapy Charité Universitätsmedizin Berlin Germany
Department of Psychiatry and Psychotherapy University Hospital LMU Munich Munich Germany
Department of Psychiatry and Psychotherapy University Medical Center Göttingen Göttingen Germany
Department of Psychiatry and Psychotherapy University of Marburg Marburg Germany
Department of Psychiatry College of Medicine National Taiwan University Taipei Taiwan
Department of Psychiatry Dalhousie University Halifax Nova Scotia Canada
Department of Psychiatry Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands
Department of Psychiatry Fujita Health University School of Medicine Toyoake Japan
Department of Psychiatry Harvard Medical School Boston MA USA
Department of Psychiatry Hospital Namsos Namsos Norway
Department of Psychiatry Hospital Universitari Vall d'Hebron Barcelona Spain
Department of Psychiatry Icahn School of Medicine at Mount Sinai New York NY USA
Department of Psychiatry Korea University College of Medicine Seoul Republic of Korea
Department of Psychiatry Massachusetts General Hospital Boston MA USA
Department of Psychiatry McGill University Montreal Québec Canada
Department of Psychiatry Nagoya University Graduate School of Medicine Nagoya Japan
Department of Psychiatry National Taiwan University Hospital Taipei Taiwan
Department of Psychiatry Sankt Olavs Hospital Universitetssykehuset i Trondheim Trondheim Norway
Department of Psychiatry Sørlandet Hospital Kristiansand Norway
Department of Psychiatry Taipei City Psychiatric Center Taipei City Hospital Taipei Taiwan
Department of Psychiatry Taipei Veterans General Hospital Taipei Taiwan
Department of Psychiatry Universidad Autonoma de Nuevo Leon Monterrey Mexico
Department of Psychiatry University of Arizona College of Medicine Phoenix Phoenix AZ USA
Department of Psychiatry University of California San Diego La Jolla CA USA
Department of Psychiatry University of Florida Gainesville FL USA
Department of Psychiatry University of Michigan Ann Arbor MI USA
Department of Psychiatry University of Münster Münster Germany
Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill NC USA
Department of Psychiatry University of Oxford Warneford Hospital Oxford UK
Department of Psychiatry University of Toronto Toronto Ontario Canada
Department of Psychiatry Washington University in Saint Louis Saint Louis MO USA
Department of Psychological Sciences University of Missouri Columbia MO USA
Department of Psychology Eberhard Karls Universität Tübingen Tubingen Germany
Department of Psychology Emory University Atlanta GA USA
Department of Quantitative Health Sciences Research Mayo Clinic Rochester MN USA
Department of Translational Research in Psychiatry Max Planck Institute of Psychiatry Munich Germany
Division of Mental Health and Addiction Oslo University Hospital Oslo Norway
Division of Psychiatry and Psychotherapeutic Medicine Medical University of Graz Graz Austria
Division of Psychiatry Centre for Clinical Brain Sciences The University of Edinburgh Edinburgh UK
Division of Psychiatry Centre for Clinical Brain Sciences University of Edinburgh Edinburgh UK
Division of Psychiatry Haukeland Universitetssjukehus Bergen Norway
Division of Psychiatry National Yang Ming Chiao Tung University Taipei Taiwan
Division of Psychiatry University College London London UK
Division of Psychiatry University of Edinburgh Edinburgh UK
eCODE Genetics Amgen Reykjavik Iceland
Estonian Genome Centre Institute of Genomics University of Tartu Tartu Estonia
Faculty of Medicine and Dentistry University of Bergen Bergen Norway
Faculty of Medicine University of Iceland Reykjavik Iceland
Faculty of Medicine University of Queensland Brisbane Queensland Australia
Flatiron Institute New York NY USA
Friedman Brain Institute Icahn School of Medicine at Mount Sinai New York NY USA
Fundació Privada d'Investigació Sant Pau Barcelona Spain
Genetic Cancer Susceptibility Group International Agency for Research on Cancer Lyon France
German Centre for Mental Health partner site Mannheim Heidelberg Ulm Mannheim Germany
HudsonAlpha Institute for Biotechnology Huntsville AL USA
Human Genetics and Computational Biomedicine Pfizer Global Research and Development Groton CT USA
Human Genetics Institute of New Jersey Rutgers University Piscataway NJ USA
Hunter Medical Research Institute New Lambtion Heights New South Wales Australia
Institute for Genomic Health SUNY Downstate Medical Center College of Medicine Brooklyn NY USA
Institute for Genomics in Health SUNY Downstate Health Sciences University Brooklyn NY USA
Institute for Translational Psychiatry University of Münster Münster Germany
Institute of Clinical Medicine University of Oslo Oslo Norway
Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden
Institute of Medical Genetics and Pathology University Hospital Basel Basel Switzerland
Institute of Medical Sciences University of Toronto Toronto Ontario Canada
Institute of Neuroscience and Medicine Research Centre Jülich Jülich Germany
Institute of Neuroscience and Physiology University of Gothenburg Gothenburg Sweden
Institute of Psychiatric Phenomics and Genomics LMU University Hospital LMU Munich Munich Germany
Instituto de Investigación Biosanitaria ibs GRANADA Granada Spain
Instituto de Salud Carlos 3 Biomedical Network Research Centre on Mental Health Madrid Spain
iPSYCH The Lundbeck Foundation Initiative for Integrative Psychiatric Research Aarhus Denmark
iSEQ Center for Integrative Sequencing Aarhus University Aarhus Denmark
JRD Data Science Janssen Research and Development Titusville NJ USA
KG Jebsen Centre for Neurodevelopmental disorders University of Oslo Oslo Norway
Landspitali University Hospital Reykjavik Iceland
Medical and Population Genetics Broad Institute Cambridge MA USA
Mental Health Department University Regional Hospital Biomedicine Institute Málaga Spain
Monash Institute of Pharmaceutical Sciences Monash University Parkville Victoria Australia
Montreal Neurological Institute and Hospital McGill University Montréal Québec Canada
Munich Cluster for Systems Neurology Munich Germany
National Centre for Register Based Research Aarhus University Aarhus Denmark
National Institute of Mental Health Klecany Czech Republic
NCRR and CIRRAU Aarhus BSS Aarhus University Aarhus Denmark
Neurogenetics Section Centre for Addiction and Mental Health Toronto Ontario Canada
Neuroscience Research Australia Sydney New South Wales Australia
Neuroscience Therapeutic Area Janssen Research and Development Titusville NJ USA
New York University New York NY USA
Nic Waals Institute Lovisenberg Diaconal Hospital Oslo Norway
NIHR Maudsley BRC King's College London London UK
Northwestern University Chicago IL USA
Oasi Research Institute IRCCS Troina Italy
Outpatient Clinic for Bipolar Disorder Altrecht Utrecht The Netherlands
Oxford Health NHS Foundation Trust Warneford Hospital Oxford UK
Population Health QIMR Berghofer Medical Research Institute Brisbane Queensland Australia
PROMENTA Research Centre Department of Psychology University of Oslo Oslo Norway
Psychiatric and Neurodevelopmental Genetics Unit Massachusetts General Hospital Boston MA USA
Psychiatry and the Behavioral Sciences University of Southern California Los Angeles CA USA
Psychiatry Brain Center UMC Utrecht Utrecht The Netherlands
Psychiatry Indiana University School of Medicine Indianapolis IN USA
Psychiatry North East London NHS Foundation Trust Ilford UK
Psychiatry Psychiatrisches Zentrum Nordbaden Wiesloch Germany
Psychiatry St Olavs University Hospital Trondheim Norway
Psychiatry University of California San Francisco San Francisco CA USA
Psychiatry University of Pennsylvania Philadelphia PA USA
Psychological Medicine University of Worcester Worcester UK
Psychosis Research Unit Aarhus University Hospital Psychiatry Risskov Denmark
Research Institute Lindner Center of HOPE Mason OH USA
Research Psychiatry Veterans Affairs San Diego Healthcare System San Diego CA USA
Rutgers Health Rutgers University Piscataway NJ USA
School of Biomedical Sciences Queensland University of Technology Brisbane Queensland Australia
School of Medicine and Public Health University of Newcastle Newcastle New South Wales Australia
School of Psychology The University of Queensland Brisbane Queensland Australia
Social Genetic and Developmental Psychiatry Centre King's College London London UK
South London and Maudsley NHS Foundation Trust Bethlem Royal Hospital Kent UK
Stanley Center for Psychiatric Research Broad Institute Cambridge MA USA
Unit of Clinical Psychiatry University Hospital Agency of Cagliari Cagliari Italy
Université Paris Est Créteil INSERM IMRB Translational Neuropsychiatry Créteil France
University Hospital of Psychiatry and Psychotherapy University of Bern Bern Switzerland
University of Liverpool Liverpool UK
University of Newcastle Newcastle New South Wales Australia
University of Queensland Brisbane Queensland Australia
VA NY Harbor Healthcare System Brooklyn NY USA
Zayed Center for Health Sciences United Arab Emirates University Al Ain United Arab Emirates
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