Identification and replication of a combined epigenetic and genetic biomarker predicting suicide and suicidal behaviors
Open accessAbstract
Considerable research suggests that suicide involves effects of genes, the environment, and their interaction. Analysis of three independent data sets of post-mortem brains revealed signs of increased methylation in one particular gene, SKA2, a finding that was extended to peripheral blood samples from other cohorts of prospectively followed individuals.
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SKA2 shows lower expression and increased promoter methylation in individuals who died by suicide; these patterns correlate with elevated waking cortisol and suicidal ideation.
“SKA2, involved in glucocorticoid receptor nuclear translocation, shows lower expression and increased promoter methylation in individuals who died by suicide; these patterns correlate with elevated waking cortisol and suicidal ideation (59).”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [59]
The Results (Gene expression and functional relevance; page not provided) report lower SKA2 expression in suicide cases. The paper links suicide to methylation at rs7208505 in the SKA2 3′UTR, not to increased promoter methylation in suicide decedents. The Results (Association of SKA2 with salivary cortisol; page not provided) associate waking cortisol with suicidal ideation and rs7208505 methylation in a separate cohort, but do not establish that the patterns in decedents correlate with elevated waking cortisol. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMethylation alterations in CRH, SKA2, BDNF, and SLC6A4 have also been implicated in suicidal behavior.
“Methylation alterations in corticotropin-releasing hormone (CRH), spindle and kinetochore-associated complex subunit 2 (SKA2), brain-derived neurotrophic factor (BDNF), and SLC6A4 have also been implicated in suicidal behavior.”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [59]
The Results (Genome-wide DNA methylation analysis and replication; page unavailable) associate SKA2 methylation variation with suicide, and the Discussion reports associations with suicidal ideation and attempts. Our copy does not establish the claimed methylation links for CRH, BDNF, or SLC6A4 (searched each gene and its expanded name). (LLM, conf=0.90)
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- Authors
- Guintivano, J., Brown, T., Newcomer, A., Jones, M., Cox, O., Maher, B. S., Eaton, W. W., Payne, J. L., Wilcox, H. C., & Kaminsky, Z. A.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Kaminsky, Zachary A.
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2014-12-01
- Volume
- 171
- Issue
- 12
- Pages
- 1287-1296
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC7081376
- OpenAlex
- W2151471104
- Cited by
- 193
- References
- 38
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 8 · 2023: 15 · 2022: 9 · 2021: 16 · 2020: 19 · 2019: 12 · 2018: 31 · 2017: 20 · 2016: 22 · 2015: 22 · 2014: 5
- FWCI
- 27.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Foundation for Suicide Prevention
- McLean Hospital
- Johns Hopkins University
- National Institute of Mental Health (NIMH K23, MH-094771, K23MH074799, MH-074799, R21MH094771, R01MH112704)
- National Institute on Drug Abuse (DA 09897, R01DA009897)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- suicide, suicidal behavior, epigenetic biomarkers, DNA methylation, SKA2, gene-environment interaction, postmortem brain, peripheral blood, biomarker prediction
- MeSH terms
- Adult, Aged, Anxiety, Cadaver, Chromosomal Proteins, Non-Histone, Female, Gene Expression Regulation, Genetic Markers, Humans, Hydrocortisone, Male, Middle Aged, Neuroglia, Neurons, Predictive Value of Tests, Saliva, Stress, Psychological, Suicide, Suicide, Attempted, Genetic Variation, Prefrontal Cortex, Sequence Analysis, DNA, DNA Methylation, Living Donors, Epigenesis, Genetic, Genome-Wide Association Study, Suicidal Ideation
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