Evidence map›Paper›PMID 34992238›Full record

SynthesisMolecular psychiatry2022

Epigenome-wide meta-analysis of PTSD symptom severity in three military cohorts implicates DNA methylation changes in genes involved in immune system and oxidative stress.

Seyma Katrinli, Adam X Maihofer, Agaz H Wani, John R Pfeiffer, Elizabeth Ketema, Andrew Ratanatharathorn, Dewleen G Baker, Marco P Boks, Elbert Geuze, Ronald C Kessler and 9 more

Open access · bronzeAbstract readMeta-Analysis
In one paragraph

Synthesis in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 5 pooled it
4.3field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 5 syntheses or guidelines pooled it, 51 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. DNA methylation GrimAge acceleration in US military veterans with PTSD.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023
    Trial
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  10. Review
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  14. Post-traumatic stress disorder: evolving conceptualization and evidence, and future research directions.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2025
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 11 institutions in 2 countries.

Seyma KatrinliDepartment of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA.ORCID http://orcid.org/0000-0003-1575-8642
Adam X MaihoferDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-4517-1623
Agaz H WaniGenomics Program, College of Public Health, University of South Florida, Tampa, FL, USA.
John R PfeifferDepartment of Psychology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Elizabeth KetemaDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Andrew RatanatharathornDepartment of Epidemiology, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0001-9855-0438
Dewleen G BakerDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-1736-9838
Marco P BoksBrain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0001-6163-7484
Elbert GeuzeBrain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0003-3479-2379
Ronald C KesslerDepartment of Health Care Policy, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4831-2305
Victoria B RisbroughDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-8347-3820
Bart P F RuttenDepartment of Psychiatry and Neuropsychology, Maastricht University Medical Centre, School for Mental Health and Neuroscience, Maastricht, The Netherlands.ORCID http://orcid.org/0000-0002-9834-6346
Murray B SteinDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Robert J UrsanoCenter for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University School of Medicine, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-1861-9173
Eric VermettenBrain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Mark W LogueNational Center for PTSD, Behavioral Science Division at VA Boston Healthcare System, Boston, MA, USA.
Caroline M NievergeltDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5766-8923
Alicia K SmithDepartment of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-8537-5156
Monica UddinGenomics Program, College of Public Health, University of South Florida, Tampa, FL, USA. monica43@usf.edu.ORCID http://orcid.org/0000-0001-7404-2068
University of California San Diego · USEmory University · USUniversity Medical Center Utrecht · NLUniversity of South Florida · USBoston University · USColumbia University · USHarvard University · USLeiden University Medical Center · NLMaastricht University Medical Centre · NLUniformed Services University of the Health Sciences · USUniversity of Illinois Urbana-Champaign · US

Funding

Modifiable Risk and Protective Factors for Suicidal Behaviors in the US ArmyU01MH087981 · NIMH · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI STEIN, MURRAY B., URSANO, ROBERT J. · 2009 to 2013
$65.0M
Psychiatric Genomics Consortium for PTSDR01MH106595 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARESTAN C KOENEN, Caroline M Nievergelt · 2016 to 2026
$8.4M
The Impact of Traumatic Stress on the Methylome: implications for PTSDR01MH108826 · NIMH · EMORY UNIVERSITY · PI LOGUE, MARK W, NIEVERGELT, CAROLINE M · 2016 to 2024
$5.8M
4/7 Psychiatric Genomics Consortium: Advancing Discovery and ImpactR01MH124847 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIEVERGELT, CAROLINE M, SEBAT, JONATHAN · 2021 to 2025
$2.1M
NIMH NIH HHS R01 MH106595NIMH NIH HHS R01 MH108826NIMH NIH HHS R01 MH124847NIMH NIH HHS U01 MH087981
6 · The paper itself

Abstract

Epigenetic factors modify the effects of environmental factors on biological outcomes. Identification of epigenetic changes that associate with PTSD is therefore a crucial step in deciphering mechanisms of risk and resilience. In this study, our goal is to identify epigenetic signatures associated with PTSD symptom severity (PTSS) and changes in PTSS over time, using whole blood DNA methylation (DNAm) data (MethylationEPIC BeadChip) of military personnel prior to and following combat deployment. A total of 429 subjects (858 samples across 2 time points) from three male military cohorts were included in the analyses. We conducted two different meta-analyses to answer two different scientific questions: one to identify a DNAm profile of PTSS using a random effects model including both time points for each subject, and the other to identify a DNAm profile of change in PTSS conditioned on pre-deployment DNAm. Four CpGs near four genes (F2R, CNPY2, BAIAP2L1, and TBXAS1) and 88 differentially methylated regions (DMRs) were associated with PTSS. Change in PTSS after deployment was associated with 15 DMRs, of those 2 DMRs near OTUD5 and ELF4 were also associated with PTSS. Notably, three PTSS-associated CpGs near F2R, BAIAP2L1 and TBXAS1 also showed nominal evidence of association with change in PTSS. This study, which identifies PTSD-associated changes in genes involved in oxidative stress and immune system, provides novel evidence that epigenetic differences are associated with PTSS.

Indexed as

Military PersonnelStress Disorders, Post-TraumaticAdaptor Proteins, Signal TransducingDNA MethylationEpigenesis, GeneticEpigenomeHumansImmune SystemMaleOxidative StressAdaptor Proteins, Signal TransducingCNPY2 protein, human

Identifiers

PMID34992238
PMCPMC9106882
OpenAlexW4205764280

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.