Genome-wide association study meta-analysis of suicide death and suicidal behavior
Open accessAbstract
Abstract Suicide is a worldwide health crisis. We aimed to identify genetic risk variants associated with suicide death and suicidal behavior. Meta-analysis for suicide death was performed using 3765 cases from Utah and matching 6572 controls of European ancestry. Meta-analysis for suicidal behavior using data across five cohorts (n = 8315 cases and 256,478 psychiatric or populational controls of European ancestry) was also performed. One locus in neuroligin 1 (NLGN1) passing the genome-wide significance threshold for suicide death was identified (top SNP rs73182688, withp = 5.48 × 10−8before andp = 4.55 × 10−8after mtCOJO analysis conditioning on MDD to remove genetic effects on suicide mediated by MDD). Conditioning on suicidal attempts did not significantly change the association strength (p = 6.02 × 10−8), suggesting suicide death specificity.NLGN1encodes a member of a family of neuronal cell surface proteins. Members of this family act as splice site-specific ligands for beta-neurexins and may be involved in synaptogenesis. The NRXN-NLGN pathway was previously implicated in suicide, autism, and schizophrenia. We additionally identifiedROBO2andZNF28associations with suicidal behavior in the meta-analysis across five cohorts in gene-based association analysis using MAGMA. Lastly, we replicated two loci including variants nearSOX5andLOC101928519associated with suicidal attempts identified in the ISGC and MVP meta-analysis using the independent FinnGen samples. Suicide death and suicidal behavior showed positive genetic correlations with depression, schizophrenia, pain, and suicidal attempt, and negative genetic correlation with educational attainment. These correlations remained significant after conditioning on depression, suggesting pleiotropic effects among these traits. Bidirectional generalized summary-data-based Mendelian randomization analysis suggests that genetic risk for the suicidal attempt and suicide death are both bi-directionally causal for MDD.
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Variants in the NLGN1 gene were linked to suicidal behavior in another large-scale GWAS.
“The NLGN1 (neuroligin 1) gene encodes a member of a family of neuronal cell surface proteins involved in synaptogenesis, and variants were linked to suicidal behavior in another large-scale GWAS (40).”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [40]
A separate meta-analysis of suicide death implicated NLGN1, with the association persisting after conditioning on attempt status.
“while a separate meta-analysis of suicide death implicated NLGN1, with the association persisting after conditioning on attempt status (40).”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [40]
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Flagged first, then by citations
Research works printed but not linked: 1
- [42]Docherty AR, Mullins N, Ashley-Koch AE, Qin XJ, Coleman J, Shabalin AA, et al. Genome-wide association study meta-analysis of suicide attempt in 43,871 cases identifies twelve genome-wide significant loci. medRxiv [Preprint] 2022.
Cited by
Sorted by citations
Salehi, M., Saeidi, M., Amanat, M., Barias, T., Anyeji, U., Alzein, O., & Gunturu, S. (2026) · Frontiers in Pediatrics · doi:10.3389/fped.2026.1738009
“At the molecular level, the largest genome-wide meta-analysis of suicide attempt identified twelve genome-wide significant loci across about 44,000 cases ( 38), while a separate meta-analysis of suicide death implicated NLGN1 , with the association persisting after conditioning on attempt status (40).”
Influential
- Authors
- 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.
- Affiliations
- Janssen Research & Development (United States) (US)
- University of Utah (US)
- Regeneron (United States) (US)
- University of Helsinki (FI)
- Virginia Commonwealth University (US)
- Corresponding author
- Li, Qingqin S.
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2022-10-17
- Volume
- 28
- Issue
- 2
- Pages
- 891-900
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC9908547
- OpenAlex
- W4306404616
- Cited by
- 68
- References
- 95
- Citations by year
- 2026: 19 · 2025: 25 · 2024: 17 · 2023: 7
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Molecular Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Työväentutkimus Vuosikirja (submittedVersion)
- Funders
- The study was supported by Janssen Research & Development, LLC
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- suicide, suicidal behavior, suicide attempts, genetic risk variants, neuroligin-1, Robo2, SOX5, genetic correlation, major depressive disorder, pleiotropy, Mendelian randomization, synaptogenesis
- MeSH terms
- Humans, Risk Factors, Suicide, Suicide, Attempted, Genome-Wide Association Study, Suicidal Ideation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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