Genome-Wide Association Study of Suicide Death and Polygenic Prediction of Clinical Antecedents
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Abstract
OBJECTIVE: Death by suicide is a highly preventable yet growing worldwide health crisis. To date, there has been a lack of adequately powered genomic studies of suicide, with no sizable suicide death cohorts available for analysis. To address this limitation, the authors conducted the first comprehensive genomic analysis of suicide death using previously unpublished genotype data from a large population-ascertained cohort. METHODS: The analysis sample comprised 3,413 population-ascertained case subjects of European ancestry and 14,810 ancestrally matched control subjects. Analytical methods included principal component analysis for ancestral matching and adjusting for population stratification, linear mixed model genome-wide association testing (conditional on genetic-relatedness matrix), gene and gene set-enrichment testing, and polygenic score analyses, as well as single-nucleotide polymorphism (SNP) heritability and genetic correlation estimation using linkage disequilibrium score regression. RESULTS: value of 0.25 (SE=0.04) and a value of 0.16 (SE=0.02) when converted to a liability scale. Notably, suicide polygenic scores were significantly predictive across training and test sets. Polygenic scores for several other psychiatric disorders and psychological traits were also predictive, particularly scores for behavioral disinhibition and major depressive disorder. CONCLUSIONS: Multiple genome-wide significant loci and genes were identified and polygenic score prediction of suicide death case-control status was demonstrated, adjusting for ancestry, in independent training and test sets. Additionally, the suicide death sample was found to have increased genetic risk for behavioral disinhibition, major depressive disorder, depressive symptoms, autism spectrum disorder, psychosis, and alcohol use disorder compared with the control sample.
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The chromosome 7 intergenic locus from ISGC stayed significant after conditioning on psychiatric disorders and was independently replicated in the MVP cohort.
“The intergenic locus on chromosome 7 remained significant after conditioning on psychiatric disorders and was independently replicated (p=3.27×10−3) (8) in the Million Veteran Program (MVP) cohort (9).”
From GWAS meta-analysis of suicide attempt: identification of 12 genome-wide significant loci and implication of genetic risks for specific health factors (2023) · cites this paper as [8]
The MVP suicide attempt GWAS found two genome-wide significant multi-ancestry loci, on chromosomes 20 and 1.
“The MVP cohort GWAS of suicide attempt (total N=409,153; 14,089 cases) resulted in two genome-wide significant multi-ancestry loci, on chromosomes 20 (index SNP: rs56817213; p=3.64×10−9) and 1 (index SNP: rs72730526; p=3.69×10−8) (8).”
From GWAS meta-analysis of suicide attempt: identification of 12 genome-wide significant loci and implication of genetic risks for specific health factors (2023) · cites this paper as [8]
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- Authors
- Docherty, A. R., Shabalin, A. A., DiBlasi, E., Monson, E., Mullins, N., Adkins, D. E., Bacanu, S.-A., Bakian, A. V., Crowell, S., Chen, D., Darlington, T. M., Callor, W. B., Christensen, E. D., Gray, D., Keeshin, B., Klein, M., Anderson, J. S., Jerominski, L., Hayward, C., Porteous, D. J., McIntosh, A., Li, Q., & Coon, H.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- Docherty, Anna R.
- ORCID
- Docherty, Anna R.
- Shabalin, Andrey A.
- DiBlasi, Emily
- Monson, Eric
- Mullins, Niamh
- Adkins, Daniel E.
- Bacanu, Silviu-Alin
- Bakian, Amanda V.
- Crowell, Sheila
- Chen, Danli
- Darlington, Todd M.
- Callor, William B.
- Christensen, Erik D.
- Gray, Douglas
- Keeshin, Brooks
- Hayward, Caroline
- Porteous, David J.
- McIntosh, Andrew
- Li, Qingqin
- Coon, Hilary
- Venue
- American Journal of Psychiatry
- Published
- 2020-10-01
- Volume
- 177
- Issue
- 10
- Pages
- 917-927
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC7872505
- OpenAlex
- W3090112529
- Cited by
- 124
- References
- 58
- Citations by year
- 2026: 14 · 2025: 21 · 2024: 20 · 2023: 17 · 2022: 22 · 2021: 26 · 2020: 4
- FWCI
- 10.10
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- American Foundation for Suicide Prevention
- National Alliance for Research on Schizophrenia and Depression
- Wellcome Trust (104036/Z/14/Z)
- Huntsman Cancer Institute
- Scottish Government (CZD/16/6)
- Scottish Funding Council (HR03006)
- National Institutes of Health (UL1TR002538)
- Chief Scientist Office, Scottish Government Health and Social Care Directorate (CZD/16/6)
- Medical Research Council (104036/Z/14/Z, MC_UU_00007/10)
- National Institute of Mental Health (R01MH123619, K01MH093731, K01MH109765, R01MH099134, R01MH122412, R01MH123489)
- National Cancer Institute (P30CA042014)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- suicide mortality, genome-wide association study, polygenic risk score, genetic risk factors, behavioral disinhibition, major depressive disorder, autism spectrum disorder, psychosis, alcoholism, mental illness, genetic correlation, suicide prevention
- MeSH terms
- Suicide, Completed, Adult, Female, Humans, Male, Scotland, Sex Factors, Utah, Linkage Disequilibrium, Genome, Human, Case-Control Studies, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Principal Component Analysis, Genome-Wide Association Study, Young Adult, Genotyping Techniques
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