Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
R01 MH121455
NIMH NIH HHS - United States
R01 MH104964
NIMH NIH HHS - United States
R01 MH123489
NIMH NIH HHS - United States
R01 MH124873
NIMH NIH HHS - United States
T32 GM007347
NIGMS NIH HHS - United States
R01 MH123451
NIMH NIH HHS - United States
T32 GM152284
NIGMS NIH HHS - United States
MRF_C0396
MRF - United Kingdom
CEP Register
R01 MH116269
NIMH NIH HHS - United States
UL1 TR002538
NCATS NIH HHS - United States
G0200243
Medical Research Council - United Kingdom
MR/L010305/1
Medical Research Council - United Kingdom
S10 OD018522
NIH HHS - United States
MR/J000914/1
Medical Research Council - United Kingdom
R01 AA027522
NIAAA NIH HHS - United States
S10 OD026880
NIH HHS - United States
R01 MH119243
NIMH NIH HHS - United States
R01 MH123619
NIMH NIH HHS - United States
PubMed
34861974
PubMed Central
PMC8851871
DOI
10.1016/j.biopsych.2021.05.029
PII: S0006-3223(21)01570-5
Knihovny.cz E-resources
- Keywords
- Genetic correlation, Genome-wide association study, Pleiotropy, Polygenicity, Suicide, Suicide attempt,
- MeSH
- Genome-Wide Association Study MeSH
- Depressive Disorder, Major * genetics MeSH
- Mental Disorders * genetics MeSH
- Polymorphism, Single Nucleotide MeSH
- Humans MeSH
- Suicide, Attempted MeSH
- Risk Factors MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
Behavioral Health Services Kaiser Permanente Washington Seattle Washington DC
BioRealm LLC Walnut California; Oregon Research Institute Eugene Oregon
Center for Applied Genomics Children's Hospital of Philadelphia Philadelphia Pennsylvania
Center for Eating Disorders at Sheppard Pratt Baltimore Maryland
Center for Research in Environmental Epidemiology Barcelona Spain
Department of Biomedical and NeuroMotor Sciences University of Bologna Bologna Italy
Department of Clinical Psychology The Chicago School of Professional Psychology Washington DC
Department of Clinical Sciences Psychiatry Umeå University Medical Faculty Umeå Sweden
Department of Environmental Epidemiology Nofer Institute of Occupational Medicine Lódz Poland
Department of Environmental Health Harvard TH Chan School of Public Health Boston Massachusetts
Department of Genetics and Genomic Biology The Hospital for Sick Children Toronto Ontario Canada
Department of Health Care Policy Harvard Medical School Boston Massachusetts
Department of Paediatric Laboratory Medicine The Hospital for Sick Children Toronto Ontario Canada
Department of Psychiatry Amsterdam UMC Vrije Universiteit and GGZ inGeest Amsterdam Netherlands
Department of Psychiatry and Behavioral Sciences Emory University School of Medicine Atlanta Georgia
Department of Psychiatry and Behavioral Sciences Stanford University Stanford California
Department of Psychiatry and Behavioral Sciences SUNY Upstate Medical University Syracuse New York
Department of Psychiatry and Neuroscience University of Gothenburg Gothenburg Sweden
Department of Psychiatry and Psychology Mayo Clinic Rochester Minnesota
Department of Psychiatry and Psychotherapy Universitätsmedizin Berlin Berlin Germany
Department of Psychiatry and Psychotherapy University Medical Center Mainz Germany
Department of Psychiatry Biomedical Research Centre University of Granada Granada Spain
Department of Psychiatry Columbia University College of Physicians and Surgeons New York New York
Department of Psychiatry Faculty of Medicine McGill University Montreal Québec Canada
Department of Psychiatry Kobe University Graduate School of Medicine Kobe Japan
Department of Psychiatry National Taiwan University Hospital and College of Medicine Taipei Taiwan
Department of Psychiatry National Taiwan University Hospital Taipei Taiwan
Department of Psychiatry UMC Utrecht Hersencentrum Utrecht the Netherlands
Department of Psychiatry Uniformed University of the Health Sciences Bethesda Maryland
Department of Psychiatry University Hospital Bellvitge IDIBELL and CIBEROBN Barcelona Spain
Department of Psychiatry University of California San Diego La Jolla California
Department of Psychiatry University of Coimbra Coimbra Portugal
Department of Psychiatry University of Iowa Iowa City Iowa
Department of Psychiatry University of Minnesota Minneapolis Minnesota
Department of Psychiatry University of North Carolina at Chapel Hill Chapel Hill North Carolina
Department of Psychiatry University of Oxford Oxford United Kingdom
Department of Psychiatry University of Utah School of Medicine Salt Lake City Utah
Department of Psychiatry Virginia Commonwealth University Richmond Virginia
Department of Psychiatry Weill Cornell Medical College New York New York
Department of Psychiatry Yokohama City University Graduate School of Medicine Yokohama Japan
Department of Psychological Medicine University of Worcester Worcester United Kingdom
Department of Psychology Florida State University Tallahassee Florida
Department of Psychology Michigan State University Lansing Michigan
Department of Surgery Faculty of Medicine University of Toronto Toronto Ontario Canada
Department of Translational Genomics University of Southern California Pasadena California
Departments of Psychiatry and Radiology Columbia University New York New York
Discipline of Psychiatry University of Adelaide Adelaide South Australia Australia
Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda Maryland
Division of Psychiatry University College London London United Kingdom
Division of Psychiatry University of Edinburgh Edinburgh United Kingdom
Duke Molecular Physiology Institute Duke University Medical Center Durham North Carolina
Eating Recovery Center Denver Colorado
Health Sciences Research Mayo Clinic Rochester Minnesota
HudsonAlpha Institute for Biotechnology Huntsville Alabama
Institute for Genetics and Molecular Medicine University of Edinburgh Edinburgh United Kingdom
Institute for Genomic Health SUNY Downstate Medical Center College of Medicine Brooklyn New York
Institute for Molecular Bioscience The University of Queensland Brisbane Queensland Australia
Institute of Health and Wellbeing University of Glasgow Glasgow United Kingdom
Institute of Psychiatry and Neuroscience of Paris INSERM U1266 Université de Paris Paris France
Institute of Psychology Psychiatry and Neuroscience King's College London London United Kingdom
Max Planck Institute of Psychiatry Munich Germany
Mental Health Department University Regional Hospital Biomedicine Institute Málaga Spain
Molecular Brain Science Centre for Addiction and Mental Health Toronto Ontario Canada
Neuroscience Janssen Research and Development LLC Titusville New Jersey
Psychiatry and Human Genetics University of Pittsburgh Pittsburgh Pennsylvania
Psychiatry Berkshire Healthcare NHS Foundation Trust Bracknell United Kingdom
Psychiatry Kaiser Permanente Northern California San Francisco California
Psychiatry North East London NHS Foundation Trust Ilford Cheshire United Kingdom
Research Institute Lindner Center of HOPE Mason Ohio
School of Psychiatry University of New South Wales Sydney New South Wales Australia
School of Psychology University of New South Wales Sydney New South Wales Australia
Social Genetic and Developmental Psychiatry Centre King's College London London United Kingdom
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