Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium - (Author)
  • Icahn School of Medicine at Mount Sinai
  • Vanderbilt University
  • Queensland Museum
  • King's College Hospital NHS Foundation Trust
  • Virginia Commonwealth University in Qatar
  • University of Northern British Columbia
  • Yale University
  • Emory University
  • University of Utah Hospital
  • Aarhus University
  • National Taiwan Normal University
  • Curtin University
  • Edinburgh Napier University
  • Charité – Universitätsmedizin Berlin
  • University of California Los Angeles Medical Center
  • Yokohama City University
  • Kobe University
  • Broad Institute of Harvard University and MIT
  • University of Michigan, Dearborn (UM–Dearborn)
  • Oregon Research Institute
  • Edinboro University of Pennsylvania
  • Center for Eating Disorders at Sheppard Pratt
  • Center for Applied Genomics
  • National Taiwan University Hospital
  • Minnesota State University Moorhead
  • GHU Paris Psychiatrie & Neuro sciences
  • University Hospital of Bellvitge
  • Hospital of the Ludwig-Maximilians-University (LMU) Munich
  • York University Toronto
  • SUNY Upstate Medical University
  • Weill Cornell Medical College in Qatar
  • University of California San Diego Health
  • Université Paris-Est Créteil
  • Eating Recovery Center Colorado
  • Florida State University
  • Heidelberg University 
  • Johns Hopkins University
  • National Institute of Mental Health (NIMH)
  • University Medical Center Göttingen
  • National Center for Tumor Diseases (NCT) Heidelberg
  • CIBER - Center for Biomedical Research Network

Abstract

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.

Details

Original languageEnglish
Pages (from-to)313-327
Number of pages15
JournalBiological psychiatry
Volume91
Issue number3
Publication statusPublished - 1 Feb 2022
Peer-reviewedYes
Externally publishedYes

External IDs

PubMedCentral PMC8851871
Scopus 85119273569

Keywords

Sustainable Development Goals

Keywords

  • Depressive Disorder, Major/genetics, Genome-Wide Association Study, Humans, Mental Disorders/genetics, Polymorphism, Single Nucleotide, Risk Factors, Suicide, Attempted