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Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR

Author

Listed:
  • Alicia K. Smith

    (Emory University, Department of Gynecology and Obstetrics
    Emory University, Department of Psychiatry & Behavioral Sciences)

  • Andrew Ratanatharathorn

    (Columbia University, Department of Epidemiology)

  • Adam X. Maihofer

    (University of California San Diego, Department of Psychiatry)

  • Robert K. Naviaux

    (University of California, The Mitochondrial and Metabolic Disease Center, Departments of Medicine, Pediatrics, and Pathology)

  • Allison E. Aiello

    (University of North Carolina, Gillings School of Global Public Health, Department of Epidemiology)

  • Ananda B. Amstadter

    (Virginia Commonwealth University, Department of Psychiatry)

  • Allison E. Ashley-Koch

    (Duke University Medical Center)

  • Dewleen G. Baker

    (University of California San Diego, Department of Psychiatry
    Veterans Affairs San Diego Healthcare System
    Veterans Affairs Center of Excellence for Stress and Mental Health)

  • Jean C. Beckham

    (VA Mid-Atlantic, Mental Illness Research, Education, and Clinical Center
    Veterans Affairs Durham Healthcare System
    Duke University Medical Center, Department of Psychiatry and Behavioral Sciences)

  • Marco P. Boks

    (University Medical Center Utrecht, Brain Center Rudolf Magnus)

  • Evelyn Bromet

    (State University of New York at Stony Brook, Epidemiology Research Group)

  • Michelle Dennis

    (VA Mid-Atlantic, Mental Illness Research, Education, and Clinical Center
    Duke University Medical Center, Department of Psychiatry and Behavioral Sciences)

  • Sandro Galea

    (Boston University, School of Public Health)

  • Melanie E. Garrett

    (Duke University Medical Center)

  • Elbert Geuze

    (University Medical Center Utrecht, Brain Center Rudolf Magnus
    Netherlands Ministry of Defence, Brain Research and Innovation Centre)

  • Guia Guffanti

    (McLean Hospital, Division of Depression and Anxiety
    Harvard Medical School)

  • Michael A. Hauser

    (Duke University Medical Center
    Duke University, Department of Medicine)

  • Seyma Katrinli

    (Emory University, Department of Gynecology and Obstetrics)

  • Varun Kilaru

    (Emory University, Department of Gynecology and Obstetrics)

  • Ronald C. Kessler

    (Harvard Medical School)

  • Nathan A. Kimbrel

    (VA Mid-Atlantic, Mental Illness Research, Education, and Clinical Center
    Veterans Affairs Durham Healthcare System
    Duke University Medical Center, Department of Psychiatry and Behavioral Sciences)

  • Karestan C. Koenen

    (Harvard T.H. Chan School of Public Health, Department of Epidemiology
    Massachusetts General Hospital, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, and Department of Psychiatry
    Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research)

  • Pei-Fen Kuan

    (State University of New York at Stony Brook, Department of Applied Mathematics and Statistics)

  • Kefeng Li

    (University of California, The Mitochondrial and Metabolic Disease Center, Department of Medicine)

  • Mark W. Logue

    (National Center for PTSD, Behavioral Science Division at VA Boston Healthcare System
    Boston University School of Medicine, Department of Psychiatry
    Boston University School of Medicine, Department of Medicine (Biomedical Genetics)
    Boston University School of Public Health, Department of Biostatistics)

  • Adriana Lori

    (Emory University, Department of Psychiatry & Behavioral Sciences)

  • Benjamin J. Luft

    (State University of New York at Stony Brook, Department of Medicine)

  • Mark W. Miller

    (National Center for PTSD, Behavioral Science Division at VA Boston Healthcare System
    Boston University School of Medicine, Department of Psychiatry)

  • Jane C. Naviaux

    (University of California, The Mitochondrial and Metabolic Disease Center, Department of Neuroscience)

  • Nicole R. Nugent

    (Brown University, Psychiatry and Human Behavior, Department of Pediatric Research)

  • Xuejun Qin

    (Duke University Medical Center)

  • Kerry J. Ressler

    (Emory University, Department of Psychiatry & Behavioral Sciences
    McLean Hospital, Division of Depression and Anxiety
    Harvard Medical School)

  • Victoria B. Risbrough

    (University of California San Diego, Department of Psychiatry
    Veterans Affairs San Diego Healthcare System
    Veterans Affairs Center of Excellence for Stress and Mental Health)

  • Bart P. F. Rutten

    (Maastricht University Medical Centre, School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology)

  • Murray B. Stein

    (University of California San Diego, Department of Psychiatry
    Veterans Affairs San Diego Healthcare System
    University of California San Diego, Department of Family Medicine and Public Health)

  • Robert J. Ursano

    (Uniformed Services University School of Medicine, Center for the Study of Traumatic Stress)

  • Eric Vermetten

    (University Medical Center Utrecht, Brain Center Rudolf Magnus
    Uniformed Services University School of Medicine, Center for the Study of Traumatic Stress
    Leiden University Medical Center, Department of Psychiatry
    Netherlands Defense Department, Research Center)

  • Christiaan H. Vinkers

    (Amsterdam UMC (location VUmc), Department of Psychiatry
    Amsterdam UMC (location VUmc), Department of Anatomy and Neurosciences)

  • Lin Wang

    (University of California, The Mitochondrial and Metabolic Disease Center, Department of Medicine)

  • Nagy A. Youssef

    (Medical College of Georgia at Augusta University, Department of Psychiatry and Human Behavior and Office of Academic Affairs)

  • Monica Uddin

    (University of South Florida, College of Public Health)

  • Caroline M. Nievergelt

    (University of California San Diego, Department of Psychiatry
    Veterans Affairs San Diego Healthcare System
    Veterans Affairs Center of Excellence for Stress and Mental Health)

Abstract

Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.

Suggested Citation

  • Alicia K. Smith & Andrew Ratanatharathorn & Adam X. Maihofer & Robert K. Naviaux & Allison E. Aiello & Ananda B. Amstadter & Allison E. Ashley-Koch & Dewleen G. Baker & Jean C. Beckham & Marco P. Boks, 2020. "Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19615-x
    DOI: 10.1038/s41467-020-19615-x
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