Genome-wide DNA methylation in suicide victims revealing impact on gene expression
Abstract
Background Suicidal behavior is a multifactorial, polygenic state that affects millions worldwide. It is a result of interplay between hereditary and environmental factors, tied together by epigenetics. Despite vast knowledge on suicidality complete mechanism and factors leading to suicide are unknown. However there is an indication between changes in DNA methylation patterns and suicidal behavior.Methods To identify differential methylation we formed a homogenous group of male suicide victims who died by hanging and control group. Altogether our study included 18 subjects in which two brain regions, Brodmann area 9 (9 suicide victims and 9 controls)) and hippocampus (6 suicide victims and 6 controls) were investigated using next-generation sequencing (NGS).Results Our results have shown several differences in methylation level between suicide victims and controls in both brain regions (>25% difference in methylation and q-value < 0.01), with gene ontology pointing towards cell structural integrity and nervous system regulation. Additional gene expression analysis identified changes in two genes, ZNF714 (p-value = 0.002) and NRIP3 (p-value = 0.046).Limitations Major limitation is small sample size. Our analysis was conducted on brain tissue including different cell types so the results are a representation of a methylation pattern for the whole brain tissue sample.Conclusions We performed a preliminary methylation study with single base pair resolution using NGS on one of the world populations with a very high suicide risk. Obtained results offer novel insights into altered methylation patterns in suicide victims, which could provide a starting point for further studies on clinical samples with highly expressed suicide risk.
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In PTSD and suicidality, early-life trauma is associated with long-lasting BDNF promoter methylation, affecting stress reactivity and fear extinction.
“Studies in PTSD and suicidality demonstrate that early-life trauma is associated with long-lasting BDNF promoter methylation, affecting stress reactivity and fear extinction”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [67]
For suicide victims, BDNF promoter hypermethylation is observed in the prefrontal cortex and hippocampus.
“for suicide victims, BDNF promoter hypermethylation is observed in the prefrontal cortex and hippocampus”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [67]
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- Authors
- Kouter, K., Zupanc, T., & Videtič Paska, A.
- Affiliations
- University of Ljubljana (SI)
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 253
- Pages
- 419-425
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W2938845993
- Cited by
- 36
- References
- 32
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 4 · 2019: 2
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Slovenian Research Agency (P1-0104, J3-7132)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- suicide, DNA methylation, epigenetics, gene expression, hanging, Brodmann area 9, hippocampus, brain tissue, suicide risk
- MeSH terms
- Adult, Brain, Cerebral Cortex, DNA, DNA-Binding Proteins, Female, Hippocampus, Humans, Male, Promoter Regions, Genetic, Suicide, Temporal Lobe, Transcription Factors, Gene Expression, Self-Injurious Behavior, DNA Methylation, Epigenesis, Genetic, Epigenomics, Suicidal Ideation
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