DNA Methylation Perturbations in Genes Involved in Polyunsaturated Fatty Acid Biosynthesis Associated with Depression and Suicide Risk
Open accessAbstract
Polyunsaturated fatty acid (PUFA) status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs) are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3). We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD) with (n = 22) and without (n = 39) history of suicide attempt, and age- and sex-matched healthy volunteers (n = 59). Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads1) and 2 (Fads2), and elongation of very long-chain fatty acids protein 5 (Elovl5), were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in Elovl5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of Elovl5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention.
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Combining GWAS with transcriptome data indicates that suicide-related genes are associated with inflammation, the HPA axis, GABA and glutamate neurotransmission, and neurogenesis.
“Combining GWASs with transcriptome data indicates that suicide-related genes are associated with inflammation, the hypothalamic-pituitary-adrenal (HPA) axis, γ-aminobutyric acid (GABA) and glutamate neurotransmission, and neurogenesis (51-56).”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [54]
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Could Epigenetics Play a Role in Suicidal Behavior in Older Age?
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Cognitive Dysfunction and Suicide
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- Authors
- Haghighi, F., Galfalvy, H., Chen, S., Huang, Y.-Y., Cooper, T. B., Burke, A. K., Oquendo, M. A., Mann, J. J., & Sublette, M. E.
- Affiliations
- James J. Peters VA Medical Center (US)
- New York State Psychiatric Institute (US)
- Icahn School of Medicine at Mount Sinai (US)
- Nathan Kline Institute for Psychiatric Research (US)
- Corresponding author
- Haghighi, Fatemeh
- Venue
- Frontiers in Neurology
- Publisher
- Frontiers Media SA
- Published
- 2015-04-28
- Volume
- 6
- Pages
- 92-92
- ISSN
- 1664-2295 (ISSN-L)
- PMC
- PMC4412056
- OpenAlex
- W1987155494
- Cited by
- 73
- References
- 49
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 8 · 2019: 6 · 2018: 20 · 2017: 6 · 2016: 8 · 2015: 3
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Neurology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- DNA methylation, polyunsaturated fatty acids, long-chain polyunsaturated fatty acids, major depressive disorder, suicide attempts, ELOVL5, FADS1, FADS2, fatty acid desaturase, fatty acid elongation, epigenetics, dietary intervention, depression
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