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

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, Evelyn Bromet, Michelle Dennis, Sandro Galea, Melanie E. Garrett, Elbert Geuze, Guia Guffanti, Michael A. Hauser, Seyma Katrinli, Varun Kilaru, Ronald C. Kessler, Nathan A. Kimbrel, Karestan C. Koenen, Pei-Fen Kuan, Kefeng Li, Mark W. Logue, Adriana Lori, Benjamin J. Luft, Mark W. Miller, Jane C. Naviaux, Nicole R. Nugent, Xuejun Qin, Kerry J. Ressler, Victoria B. Risbrough, Bart P. F. Rutten, Murray B. Stein, Robert J. Ursano, Eric Vermetten, Christiaan H. Vinkers, Lin Wang, Nagy A. Youssef, Monica Uddin and Caroline M. Nievergelt
Additional contact information
Alicia K. Smith: Emory University, Department of Gynecology and Obstetrics
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
Jean C. Beckham: VA Mid-Atlantic, Mental Illness Research, Education, and Clinical Center
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
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
Guia Guffanti: McLean Hospital, Division of Depression and Anxiety
Michael A. Hauser: Duke University Medical Center
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
Karestan C. Koenen: Harvard T.H. Chan School of Public Health, Department of Epidemiology
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
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
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
Victoria B. Risbrough: University of California San Diego, Department of Psychiatry
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
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
Christiaan H. Vinkers: Amsterdam UMC (location VUmc), Department of Psychiatry
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

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19615-x

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