Evidence map›Paper›PMID 39696436›Full record

SynthesisGenome medicine2024

Epigenome-wide association studies identify novel DNA methylation sites associated with PTSD: a meta-analysis of 23 military and civilian cohorts.

Seyma Katrinli, Agaz H Wani, Adam X Maihofer, Andrew Ratanatharathorn, Nikolaos P Daskalakis, Janitza Montalvo-Ortiz, Diana L Núñez-Ríos, Anthony S Zannas, Xiang Zhao, Allison E Aiello and 75 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Genome medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
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

18 citing papers in PubMed.

  1. Article
  2. Article
  3. Acute stress induces changes in epigenome-wide DNA methylation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  4. Article
  5. Article
  6. Multi-ancestry epigenome wide association study of generalized anxiety disorder.medRxiv : the preprint server for health sciences · 2026
    Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
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  15. Article
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  18. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

85 authors.

Seyma KatrinliDepartment of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA.
Agaz H WaniGenomics Program, College of Public Health, University of South Florida, Tampa, FL, USA.
Adam X MaihoferDepartment of Psychiatry, University of California San Diego, La Jolla, CA, San Diego, USA.
Andrew RatanatharathornDepartment of Epidemiology, Columbia University Mailmain School of Public Health, New York, NY, USA.
Nikolaos P DaskalakisStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Janitza Montalvo-OrtizU.S. Department of Veterans Affairs National Center of Posttraumatic Stress Disorder, Clinical Neurosciences Division, West Haven, CT, USA.
Diana L Núñez-RíosU.S. Department of Veterans Affairs National Center of Posttraumatic Stress Disorder, Clinical Neurosciences Division, West Haven, CT, USA.
Anthony S ZannasCarolina Stress Initiative, University of North Carolina at Chapel Hill, NC, Chapel Hill, USA.
Xiang ZhaoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Allison E AielloRobert N. Butler Columbia Aging Center, Department of Epidemiology, Columbia University, New York, NY, USA.
Allison E Ashley-KochDuke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
Diana AvetyanDepartment of Psychiatry, University of California San Diego, La Jolla, CA, San Diego, USA.
Dewleen G BakerDepartment of Psychiatry, University of California San Diego, La Jolla, CA, San Diego, USA.
Jean C BeckhamDepartment of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
Marco P BoksDepartment of Psychiatry, Brain Center University Medical Center Utrecht, Utrecht, UT, NL, Netherlands.
Leslie A BrickDepartment of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.
Evelyn BrometEpidemiology Research Group, State University of New York at Stony Brook, Stony Brook, NY, USA.
Frances A ChampagneDepartment of Psychology, The University of Texas at Austin, Austin, TX, USA.
Chia-Yen ChenBiogen Inc, Translational Sciences, Cambridge, MA, USA.
Shareefa DalvieDepartment of Pathology, University of Cape Town, Western Province, Cape Town, ZA, South Africa.
Michelle F DennisDepartment of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
Segun FatumoMRC/UVRI and London School of Hygiene and Tropical Medicine, The African Computational Genomics (TACG) Research Group, Entebbe, Wakiso, Uganda.
Catherine FortierDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA.
Sandro GaleaSchool of Public Health, Boston University, Boston, MA, USA.
Melanie E GarrettDuke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
Elbert GeuzeBrain Research and Innovation Centre, Netherlands Ministry of Defence, Utrecht, UT, NL, Netherlands.
Gerald GrantDepartment of Neurosurgery, Duke University School of Medicine, Durham, NC, USA.
Michael A HauserDepartment of Medicine, Duke University School of Medicine, Durham, NC, USA.
Jasmeet P HayesDepartment of Psychology, The Ohio State University, Columbus, OH, USA.
Sian M J HemmingsDepartment of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Western Cape, Cape Town, ZA, South Africa.
Bertrand Russel HuberDepartment of Neurology, Boston University School of Medicine, Boston, MA, USA.
Aarti JajooStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Stefan JansenCollege of Medicine and Health Sciences, University of Rwanda, Kigali, RW, Rwanda.
Ronald C KesslerDepartment of Health Care Policy, Harvard Medical School, Boston, MA, USA.
Nathan A KimbrelDepartment of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
Anthony P KingInstitute for Behavioral Medicine Research, The Ohio State University College of Medicine, Columbus, OH, USA.
Joel E KleinmanDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nastassja KoenDepartment of Psychiatry & Mental Health, University of Cape Town, Western Province, Cape Town, ZA, South Africa.
Karestan C KoenenDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Pei-Fen KuanDepartment of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA.
Israel LiberzonDepartment of Psychiatry and Behavioral Sciences, Texas A&M University College of Medicine, Bryan, TX, USA.
Sarah D LinnstaedtDepartment of Anesthesiology, University of North Carolina at Chapel Hill, NC, Chapel Hill, USA.
Adriana LoriDepartment of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA.
Benjamin J LuftDepartment of Medicine, Stony Brook University, Stony Brook, NY, USA.
Jurjen J LuykxAmsterdam Neuroscience Research Institute Stress & Sleep Program, Amsterdam University Medical Center, Amsterdam, NH, Netherlands.
Christine E MarxDepartment of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
Samuel A McLeanDepartment of Psychiatry, UNC Institute for Trauma Recovery, NC, Chapel Hill, USA.
Divya MehtaCentre for Genomics and Personalised Health, Queensland University of Technology, Kelvin Grove, QLD, AU, Brisbane, Australia.
William MilbergGRECC/TRACTS, VA Boston Healthcare System, Boston, MA, USA.
Mark W MillerBiomedical Genetics & Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Mary S MuffordDepartment of Psychiatry and Mental Health, University of Cape Town, Western Province, Cape Town, ZA, South Africa.
Clarisse MusanabaganwaResearch Innovation and Data Science Division, Rwanda Biomedical Center, Kigali, Rwanda.
Jean MutabarukaDepartment of Clinical Psychology, University of Rwanda, Huye, RW, Rwanda.
Leon MutesaCollege of Medicine and Health Sciences, University of Rwanda, Kigali, RW, Rwanda.
Charles B NemeroffDepartment of Psychology, The University of Texas at Austin, Austin, TX, USA.
Nicole R NugentDepartment of Emergency Medicine, Alpert Brown Medical School, Providence, RI, USA.
Holly K OrcuttDepartment of Psychology, Northern Illinois University, DeKalb, IL, USA.
Xue-Jun QinDuke Molecular Physiology Institute, Duke University, Durham, NC, USA.
Sheila A M RauchDepartment of Psychiatry & Behavioral Sciences, Emory University, Atlanta, GA, USA.
Kerry J ResslerDepartment of Psychiatry, Harvard Medical School, Boston, MA, USA.
Victoria B RisbroughDepartment of Psychiatry, University of California San Diego, La Jolla, CA, San Diego, USA.
Eugène RutembesaClinical Psychology, University of Rwanda, Kigali, RW, Rwanda.
Bart P F RuttenDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht Universitair Medisch Centrum, Maastricht, Limburg, NL, Netherlands.
Soraya SeedatDepartment of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Western Cape, Cape Town, ZA, South Africa.
Dan J SteinDepartment of Psychiatry & Mental Health, University of Cape Town, Western Province, Cape Town, ZA, South Africa.
Murray B SteinDepartment of Psychiatry, University of California San Diego, La Jolla, CA, San Diego, USA.
Sylvanus ToikumoDepartment of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Western Cape, Cape Town, ZA, South Africa.
Robert J UrsanoDepartment of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University, Bethesda, MD, USA.
Annette UwinezaCollege of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda.
Mieke H VerfaellieDepartment of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
Eric VermettenDepartment of Psychiatry, Leiden University Medical Center, Leiden, ZH, NL, Netherlands.
Christiaan H VinkersDepartment of Anatomy and Neurosciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, Holland, Netherlands.
Erin B WareSurvey Research Center, University of Michigan, Ann Arbor, MI, USA.
Derek E WildmanCollege of Public Health, University of South Florida, Tampa, FL, USA.
Erika J WolfNational Center for PTSD, VA Boston Healthcare System, Boston, MA, USA.
Ross McD YoungSchool of Clinical Sciences, Queensland University of Technology, Kelvin Grove, QLD, AU, Brisbane, Australia.
Ying ZhaoInstitute for Trauma Recovery, University of North Carolina at Chapel Hill, NC, Chapel Hill, USA.
Leigh L van den HeuvelDepartment of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Western Cape, Cape Town, ZA, South Africa.
PGC-PTSD Epigenetics Workgroup
PsychENCODE PTSD Brainomics Project
Traumatic Stress Brain Research Group
Monica UddinUniversity of South Florida College of Public Health, Genomics Program, Tampa, FL, USA.
Caroline M NievergeltDepartment of Psychiatry, University of California San Diego, La Jolla, CA, San Diego, USA.
Alicia K SmithDepartment of Gynecology and Obstetrics, Emory University, Atlanta, GA, USA.
Mark W LogueDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA. loguem@bu.edu.

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Michigan Institute for Clinical and Health Research (MCHR)UL1TR000433 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MASHOUR, GEORGE ALEXANDER · 2012 to 2016
$49.9M
Transforming Translational Science and Education to Benefit Human HealthUL1TR000043 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY · 2012 to 2015
$26.8M
Longitudinal Assessment of Post-traumatic SyndromesU01MH110925 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KESSLER, RONALD C, KOENEN, KARESTAN C · 2016 to 2020
$25.8M
Training Program in Psychiatric Genetics and Translational ResearchT32MH017119 · NIMH · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI KARESTAN C KOENEN, Jukka-Pekka Onnela · 1985 to 2026
$8.9M
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
Epigenomic Predictors of PTSD and Traumatic Stress in an African American CohortR01MD011728 · NIMHD · UNIVERSITY OF SOUTH FLORIDA · PI AIELLO, ALLISON E, UDDIN, MONICA · 2017 to 2025
$5.7M
2/3 Understanding PTSD through Postmortem Targeted Brain Multi-omicsR01MH117291 · NIMH · LIEBER INSTITUTE, INC. · PI Joel Edward Kleinman · 2018 to 2026
$5.2M
Site 3/3, Understanding PTSD through Postmortem Targeted Brain MultiomicsR01MH117292 · NIMH · MCLEAN HOSPITAL · PI Nikolaos Daskalakis, KERRY J. RESSLER · 2018 to 2026
$5.0M
Emory University BIRCWH ProgramK12HD085850 · NICHD · EMORY UNIVERSITY · PI OFOTOKUN, IGHOVWERHA, STERK, CLAIRE E · 2015 to 2023
$4.4M
1/3 Understanding PTSD through Postmortem Targeted Brain Multi-omicsR01MH117293 · NIMH · UNIVERSITY OF TEXAS AT AUSTIN · PI CHARLES B NEMEROFF · 2018 to 2026
$4.3M
Bill and Melinda Gates Foundation OPP 1017641BLRD VA I01 BX002577BLRD VA I01 BX003477BLRD VA I21 BX005872BLRD VA IK6 BX006186CSRD VA I01 CX000431CSRD VA I01 CX001276CSRD VA IK2 CX000525CSRD VA IK2 CX002343CSRD VA IK6 CX002767National Institute of Child Health and Human Development K12HD085850NCATS NIH HHS UL1 TR000433NCATS NIH HHS UL1TR000433PEC-PTSDNCATS NIH HHS UL1 TR001863NCCDPHP CDC HHS U01OH012466Nederlandse Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek 91718336Nederlandse Organisatie voor Wetenschappelijk Onderzoek 09150171910042NIA NIH HHS 1R03AG051877NIA NIH HHS 1R21AG061367NIA NIH HHS R03 AG051877NIA NIH HHS R21 AG061367NIA NIH HHS RF1 AG068121NIA NIH HHS RF1AG068121NICHD NIH HHS K12 HD085850NICHD NIH HHS R15 HD049907NIDA NIH HHS 1DP1DA058737NIDA NIH HHS DP1 DA058737NIDA NIH HHS R21 DA050160NIDA NIH HHS R21DA050160NIMHD NIH HHS R01 MD011728NIMHD NIH HHS R01MD011728NIMH NIH HHS 1R15HD049907-01A1NIMH NIH HHS 1R15MH099521-01NIMH NIH HHS 5R01MH079806NIMH NIH HHS 5R21MH085436-02NIMH NIH HHS R01 MH079806NIMH NIH HHS R01 MH093500NIMH NIH HHS R01MH093500NIMH NIH HHS R01 MH105379NIMH NIH HHS R01MH105379NIMH NIH HHS R01 MH106595NIMH NIH HHS R01MH106595NIMH NIH HHS R01 MH108826NIMH NIH HHS R01MH108826NIMH NIH HHS R01 MH117291NIMH NIH HHS R01MH117291NIMH NIH HHS R01 MH117292NIMH NIH HHS R01MH117292NIMH NIH HHS R01 MH117293NIMH NIH HHS R01MH117293NIMH NIH HHS R15 MH099521NIMH NIH HHS R21 MH085436NIMH NIH HHS R21 MH102834NIMH NIH HHS R21MH102834NIMH NIH HHS T32 MH017119NIMH NIH HHS U01 MH110925NIMH NIH HHS U01MH110925NIMH NIH HHS U01 MH115485NIMH NIH HHS U01MH115485NIOSH CDC HHS U01 OH012466ORD VA B9254-CU.S. Department of Defense W81XWH-11-1-0073U.S. Department of Veterans Affairs 1I01CX001276-01A2U.S. Department of Veterans Affairs 5I01CX000431U.S. Department of Veterans Affairs B3001-CU.S. Department of Veterans Affairs BX005872U.S. Department of Veterans Affairs BX006186U.S. Department of Veterans Affairs I01BX002577U.S. Department of Veterans Affairs I01BX003477U.S. Department of Veterans Affairs IK2CX000525U.S. Department of Veterans Affairs lK6BX003777
6 · The paper itself

Abstract

backgroundThe occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at multiple CpG loci across the genome. Moreover, these effects can be shared or specific to both central and peripheral tissues. Here, we aim to identify blood DNAm differences associated with PTSD and characterize the underlying biological mechanisms by examining the extent to which they mirror associations across multiple brain regions.

methodsAs the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup, we conducted the largest cross-sectional meta-analysis of epigenome-wide association studies (EWASs) of PTSD to date, involving 5077 participants (2156 PTSD cases and 2921 trauma-exposed controls) from 23 civilian and military studies. PTSD diagnosis assessments were harmonized following the standardized guidelines established by the PGC-PTSD Workgroup. DNAm was assayed from blood using Illumina HumanMethylation450 or MethylationEPIC (850 K) BeadChips. Within each cohort, DNA methylation was regressed on PTSD, sex (if applicable), age, blood cell proportions, and ancestry. An inverse variance-weighted meta-analysis was performed. We conducted replication analyses in tissue from multiple brain regions, neuronal nuclei, and a cellular model of prolonged stress.

resultsWe identified 11 CpG sites associated with PTSD in the overall meta-analysis (1.44e - 09 < p < 5.30e - 08), as well as 14 associated in analyses of specific strata (military vs civilian cohort, sex, and ancestry), including CpGs in AHRR and CDC42BPB. Many of these loci exhibit blood-brain correlation in methylation levels and cross-tissue associations with PTSD in multiple brain regions. Out of 9 CpGs annotated to a gene expressed in blood, methylation levels at 5 CpGs showed significant correlations with the expression levels of their respective annotated genes.

conclusionsThis study identifies 11 PTSD-associated CpGs and leverages data from postmortem brain samples, GWAS, and genome-wide expression data to interpret the biology underlying these associations and prioritize genes whose regulation differs in those with PTSD.

Indexed as

CpG IslandsDNA MethylationEpigenesis, GeneticEpigenomeGenome-Wide Association StudyMilitary PersonnelStress Disorders, Post-TraumaticAdultFemaleHumansMaleDNA methylationGene expressionGWASPostmortem brainPTSDTrauma

Identifiers

PMID39696436
PMCPMC11658418

What Socratic holds

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Registered trials

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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.