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Cited by 238Suicide and Self-Harm StudiesGenetic Associations and EpidemiologySchizophrenia research and treatment

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

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Mullins, Niamh, Kang, JooEun, Campos, Adrian I., Coleman, Jonathan R.I., Edwards, Alexis C., Galfalvy, Hanga, Levey, Daniel F., Lori, Adriana +1115 more·2022·Biological Psychiatry
DOI 10.1016/j.biopsych.2021.05.029PMC PMC8851871

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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.

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Mullins, N., Kang, J., Campos, A. I., Coleman, J. R. I., Edwards, A. C., Galfalvy, H., Levey, D. F., Lori, A., Shabalin, A., Starnawska, A., Su, M.-H., Watson, H. J., Adams, M., Awasthi, S., Gandal, M., Hafferty, J. D., Hishimoto, A., Kim, M., Okazaki, S., Otsuka, I., Ripke, S., Ware, E. B., Bergen, A. W., Berrettini, W. H., Bohus, M., Brandt, H., Chang, X., Chen, W. J., Chen, H.-C., Crawford, S., Crow, S., DiBlasi, E., Duriez, P., Fernández-Aranda, F., Fichter, M. M., Gallinger, S., Glatt, S. J., Gorwood, P., Guo, Y., Hakonarson, H., Halmi, K. A., Hwu, H.-G., Jain, S., Jamain, S., Jiménez-Murcia, S., Johnson, C., Kaplan, A. S., Kaye, W. H., Keel, P. K., Kennedy, J. L., Klump, K. L., Li, D., Liao, S.-C., Lieb, K., Lilenfeld, L., Liu, C.-M., Magistretti, P. J., Marshall, C. R., Mitchell, J. E., Monson, E. T., Myers, R. M., Pinto, D., Powers, A., Ramoz, N., Roepke, S., Rozanov, V., Scherer, S. W., Schmahl, C., Sokolowski, M., Strober, M., Thornton, L. M., Treasure, J., Tsuang, M. 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Affiliations
  • Vanderbilt University (US)
  • Virginia Commonwealth University (US)
  • Columbia University (US)
  • Yale University (US)
  • Emory University (US)
  • University of Utah (US)
  • Aarhus University (DK)
  • National Taiwan University (TW)
  • University of Edinburgh (GB)
  • Yokohama City University (JP)
  • Kobe University (JP)
  • University of Michigan (US)
  • Children's Hospital of Philadelphia (US)
  • National Health Research Institutes (TW)
  • National Taiwan University Hospital (TW)
  • Inserm (FR)
  • SUNY Upstate Medical University (US)
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ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2022-02
Volume
91
Issue
3
Pages
313-327
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2021.05.029
PMC
PMC8851871
OpenAlex
W3197156699
Cited by
238
References
23
Citations by year
2026: 33 · 2025: 59 · 2024: 51 · 2023: 47 · 2022: 41 · 2021: 7
FWCI
24.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry (publishedVersion, cc-by-nc-nd)
  • UWA Profiles and Research Repository (UWA) (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
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  • Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by-nc-nd)
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  • Florence Research (University of Florence) (submittedVersion, other-oa)
  • Työväentutkimus Vuosikirja (submittedVersion, cc-by-nc-nd)
  • Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
  • Site cant be reached (submittedVersion, cc-by-nc-nd)
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  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by-nc-nd)
  • IUScholarWorks (Indiana University) (submittedVersion, cc-by-nc-nd)
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  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • RWTH Publications (RWTH Aachen)
Funders
  • National Alliance for Research on Schizophrenia and Depression
  • NIH (R01MH116269, R01MH121455, S10OD018522, S10OD026880)
  • NIGMS (T32GM007347)
  • Division of Materials Research
  • Brain and Behavior Research Foundation
Topics
  • Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
suicide attempts, genetic architecture, mental illness, major depressive disorder, major histocompatibility complex, genetic correlation, risk-taking, smoking, sleep disorders, socioeconomic status, educational attainment, reproductive traits, pain, suicide risk factors
MeSH terms
Mental Disorders, Major Depressive Disorder, Depressive Disorder, Major, Humans, Risk Factors, Suicide, Attempted, Polymorphism, Single Nucleotide, Genome-Wide Association Study

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