Genome-wide DNA methylation meta-analysis in the brains of suicide completers
Open accessAbstract
Suicide is the second leading cause of death globally among young people representing a significant global health burden. Although the molecular correlates of suicide remains poorly understood, it has been hypothesised that epigenomic processes may play a role. The objective of this study was to identify suicide-associated DNA methylation changes in the human brain by utilising previously published and unpublished methylomic datasets. We analysed prefrontal cortex (PFC, n = 211) and cerebellum (CER, n = 114) DNA methylation profiles from suicide completers and non-psychiatric, sudden-death controls, meta-analysing data from independent cohorts for each brain region separately. We report evidence for altered DNA methylation at several genetic loci in suicide cases compared to controls in both brain regions with suicide-associated differentially methylated positions enriched among functional pathways relevant to psychiatric phenotypes and suicidality, including nervous system development (PFC) and regulation of long-term synaptic depression (CER). In addition, we examined the functional consequences of variable DNA methylation within a PFC suicide-associated differentially methylated region ( PSORS1C3 DMR ) using a dual luciferase assay and examined expression of nearby genes. DNA methylation within this region was associated with decreased expression of firefly luciferase but was not associated with expression of nearby genes, PSORS1C3 and POU5F1 . Our data suggest that suicide is associated with DNA methylation, offering novel insights into the molecular pathology associated with suicidality.
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Altered genome-wide DNA methylation occurs at several loci in the prefrontal cortex and cerebellum and more globally in the brain of suicide decedents compared with controls.
“Altered genome-wide DNA methylation reveals alteration at several genetic loci in the prefrontal cortex (PFC) and cerebellum, and more globally in the brain in suicide decedents compared with control subjects (62-64).”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [62]
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- [47]Klug M Rehli M Functional analysis of promoter CPGmethylation using a CpG-free luciferase reporter vector Epigenetics 2006 1 127 130 17965610
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A brain-centric model of suicidal behavior
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- Authors
- Policicchio, S., Washer, S., Viana, J., Iatrou, A., Burrage, J., Hannon, E., Turecki, G., Kaminsky, Z., Mill, J., Dempster, E. L., & Murphy, T. M.
- Affiliations
- University of Exeter (GB)
- Rush University Medical Center (US)
- McGill University (CA)
- Johns Hopkins University (US)
- Corresponding author
- Murphy, Therese M.
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2020-02-19
- Volume
- 10
- Issue
- 1
- Pages
- 69-69
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC7031296
- OpenAlex
- W3007111333
- Cited by
- 61
- References
- 80
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 6 · 2023: 12 · 2022: 6 · 2021: 10 · 2020: 4
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open Research Exeter (University of Exeter) (publishedVersion, cc-by)
- Arrow - TU Dublin (Technological University Dublin) (submittedVersion, cc-by-nc-sa)
- Figshare (submittedVersion)
- Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion, cc-by)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- Funders
- Brain and Behavior Research Foundation (MR/K013807/1)
- Fonds de Recherche du Québec-Société et Culture (NA)
- Fondation Brain Canada (NA)
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH 1R21MH094771)
- RCUK | MRC | Medical Research Foundation (MR/K013807/1)
- 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, prefrontal cortex, cerebellum, differentially methylated regions, Oct4, synaptic depression, brain development, gene expression regulation
- MeSH terms
- Adolescent, Brain, Humans, Proteins, Suicide, Genome, DNA Methylation, Epigenesis, Genetic, Epigenomics, RNA, Long Noncoding
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.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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