Cited by 103Posttraumatic Stress Disorder ResearchEpigenetics and DNA MethylationStress Responses and Cortisol

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An epigenome-wide DNA methylation study of PTSD and depression in World Trade Center responders

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Kuan, P-F, Waszczuk, M A, Kotov, R, Marsit, C J, Guffanti, G, Gonzalez, A, Yang, X, Koenen, K, Bromet, E, Luft, B J·2017·Translational Psychiatry

DOI 10.1038/tp.2017.130PMC PMC5537648

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Abstract

Previous epigenome-wide association studies (EWAS) of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) have been inconsistent. This may be due to small sample sizes, and measurement and tissue differences. The current two EWA analyses of 473 World Trade Center responders are the largest to date for both PTSD and MDD. These analyses investigated DNA methylation patterns and biological pathways influenced by differentially methylated genes associated with each disorder. Methylation was profiled on blood samples using Illumina 450 K Beadchip. Two EWA analyses compared current versus never PTSD, and current versus never MDD, adjusting for cell types and demographic confounders. Pathway and gene set enrichment analyses were performed to understand the complex biological systems of PTSD and MDD. No significant epigenome-wide associations were found for PTSD or MDD at an FDR P<0.05. The majority of genes with differential methylation at a suggestive threshold did not overlap between the two disorders. Pathways significant in PTSD included a regulator of synaptic plasticity, oxytocin signaling, cholinergic synapse and inflammatory disease pathways, while only phosphatidylinositol signaling and cell cycle pathways emerged in MDD. The failure of the current EWA analyses to detect significant epigenome-wide associations is in contrast with disparate findings from previous, smaller EWA and candidate gene studies of PTSD and MDD. Enriched gene sets involved in several biological pathways, including stress response, inflammation and physical health, were identified in PTSD, supporting the view that multiple genes play a role in this complex disorder.

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Authors: Kuan, P.-F., Waszczuk, M. A., Kotov, R., Marsit, C. J., Guffanti, G., Gonzalez, A., Yang, X., Koenen, K., Bromet, E., & Luft, B. J.
Affiliations: Stony Brook University (US)
Emory University (US)
Harvard University (US)
Corresponding author: Luft, B J
ORCID: Waszczuk, M A
Kotov, R
Marsit, C J
Gonzalez, A
Yang, X
Koenen, K
Bromet, E
Luft, B J
Venue: Translational Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2017-06-27
Volume: 7
Issue: 6
Pages: e1158-e1158
ISSN: 2158-3188 (ISSN-L)
DOI: 10.1038/tp.2017.130
PMC: PMC5537648
OpenAlex: W2634894186
Cited by: 103
References: 80
Citations by year: 2026: 4 · 2025: 7 · 2024: 10 · 2023: 8 · 2022: 17 · 2021: 16 · 2020: 15 · 2019: 12 · 2018: 13 · 2017: 1
FWCI: 13.91
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/4.0 (tdm)
creativecommons.org/licenses/by-nc-nd/4.0 (vor)
Locations: Translational Psychiatry (publishedVersion, cc-by-nc-nd)
PubMed Central (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: Stony Brook University
Centers for Disease Control and Prevention
National Institute for Occupational Safety and Health (U01OH010416, U01 OH010416-01)
Topics: Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: post-traumatic stress disorder, major depressive disorder, DNA methylation, epigenome-wide association study, World Trade Center responders, differentially methylated genes, gene set enrichment analysis, synaptic plasticity, oxytocin signaling, cholinergic synapses, phosphoinositide signaling, cell cycle, stress response, inflammation
MeSH terms: Major Depressive Disorder, Depressive Disorder, Major, Humans, Male, Middle Aged, Stress Disorders, Post-Traumatic, Signal Transduction, CpG Islands, DNA Methylation, Epigenesis, Genetic, September 11 Terrorist Attacks, Genome-Wide Association Study, Epigenomics, Emergency Responders

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An epigenome-wide DNA methylation study of PTSD and depression in World Trade Center responders

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