Genetics of suicide attempts in individuals with and without mental disorders: a population-based genome-wide association study
Open accessAbstract
Family studies have shown an aggregation of suicidal behavior in families. Yet, molecular studies are needed to identify loci accounting for genetic heritability. We conducted a genome-wide association study and estimated single nucleotide polymorphisms (SNP) heritability for a suicide attempt. In a case-cohort study, national data on all individuals born in Denmark after 1981 and diagnosed with severe mental disorders prior to 2013 ( n = 57,377) and individuals from the general population ( n = 30,000) were obtained. After quality control, the sample consisted of 6024 cases with an incidence of suicide attempt and 44,240 controls with no record of a suicide attempt. Suggestive associations between SNPs, rs6880062 ( p -value: 5.4 × 10 −8 ) and rs6880461 ( p -value: 9.5 × 10 −8 ), and suicide attempt were identified when adjusting for socio-demographics. Adjusting for mental disorders, three significant associations, all on chromosome 20, were identified: rs4809706 ( p -value: 2.8 × 10 −8 ), rs4810824 ( p -value: 3.5 × 10 −8 ), and rs6019297 ( p -value: 4.7 × 10 8 ). Sub-group analysis of cases with affective disorders revealed SNPs associated with suicide attempts when compared to the general population for gene PDE4B. All SNPs explained 4.6% [CI-95: 2.9–6.3%] of the variation in suicide attempt. Controlling for mental disorders reduced the heritability to 1.9% [CI-95: 0.3–3.5%]. Affective and autism spectrum disorders exhibited a SNP heritability of 5.6% [CI-95: 1.9–9.3%] and 9.6% [CI-95: 1.1–18.1%], respectively. Using the largest sample to date, we identified significant SNP associations with suicide attempts and support for a genetic transmission of suicide attempt, which might not solely be explained by mental disorders.
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Candidate-gene-based studies and GWAS have not produced consistent results, with genes of interest frequently failing to pass rigorous reproducibility and significance testing.
“overall, candidate-gene-based studies 44,45 and GWAS 30,40,46-49 have not produced consistent results, with genes of interest frequently failing to pass rigorous reproducibility and significance testing.”
From Suicide and suicide risk (2019) · cites this paper as [46]
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Li, Q. S., Shabalin, A. A., DiBlasi, E., Gopal, S., Canuso, C. M., FinnGen, I. S. G. C., Palotie, A., Drevets, W. C., Docherty, A. R., & Coon, H. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01828-9 · Cited by 68 · see citing works
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- Authors
- Erlangsen, A., Appadurai, V., Wang, Y., Turecki, G., Mors, O., Werge, T., Mortensen, P. B., Starnawska, A., Børglum, A. D., Schork, A., Nudel, R., Bækvad-Hansen, M., Bybjerg-Grauholm, J., Hougaard, D. M., Thompson, W. K., Nordentoft, M., & Agerbo, E.
- Affiliations
- Australian National University (AU)
- Sankt Hans Hospital (DK)
- University of Oslo (NO)
- Douglas Mental Health University Institute (CA)
- Aarhus University Hospital (DK)
- University of Copenhagen (DK)
- Aarhus University (DK)
- Statens Serum Institut (DK)
- Corresponding author
- Erlangsen, Annette
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2018-08-16
- Volume
- 25
- Issue
- 10
- Pages
- 2410-2421
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC7515833
- OpenAlex
- W2885057788
- Cited by
- 157
- References
- 76
- Citations by year
- 2026: 3 · 2025: 18 · 2024: 21 · 2023: 25 · 2022: 24 · 2021: 30 · 2020: 19 · 2019: 15 · 2018: 2
- FWCI
- 19.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- Funders
- Lundbeckfonden (R102-A9118, R155-2014-1724)
- 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, heritability, single nucleotide polymorphisms, PDE4B, chromosome 20, mood disorders, autism spectrum disorder, mental illness, genetic loci
- MeSH terms
- Adolescent, Adult, Mental Disorders, Female, Humans, Male, Suicide, Attempted, Cohort Studies, Mood Disorders, Genome-Wide Association Study, Young Adult, Suicidal Ideation
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