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

INTRuST Clinical Consortium; VA Mid-Atlantic MIRECC Workgroup; PGC PTSD Epigenetics Workgroup

doi:10.1038/s41467-020-19615-x

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

INTRuST Clinical Consortium
, VA Mid-Atlantic MIRECC Workgroup
, PGC PTSD Epigenetics Workgroup

Emory University
Columbia University
University of California at San Diego
University of North Carolina at Chapel Hill
Virginia Commonwealth University
Duke University
Department of Veterans Affairs
VA Medical Center
VA Mid-Atlantic Mental Illness Research
Veterans Affairs Durham Healthcare System
Utrecht University
Stony Brook University
Boston University
Brain Research and Innovation Centre
McLean Hospital
Harvard University
Massachusetts General Hospital
Broad Institute
Brown University
Maastricht University
Uniformed Services University of the Health Sciences
Leiden University
Research Center
Arq Psychotrauma Expert Group
Department of Psychiatry
Augusta University
Stanford University
Indiana University
Riverside University Health System Medical Center
University of Louisville
University of Pittsburgh
Medical University of South Carolina
Salisbury Veterans Affairs Health Care System
Wake Forest University
Baylor College of Medicine
Richmond Veterans Affairs Health Care System
Virginia College of Osteopathic Medicine
University of Cape Town
Cohen Veterans Bioscience
Icahn School of Medicine at Mount Sinai
Amsterdam UMC - University of Amsterdam
De Bascule
Stellenbosch University
University of Wisconsin-Madison
University of Aberdeen
Yale University
University of Illinois at Urbana-Champaign
University of Iowa
Butler Hospital
University of South Florida

Research output: Contribution to journal › Article › peer-review

101 Citations (Scopus)

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.

Original language	English
Article number	5965
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-19615-x
Publication status	Published - 1 Dec 2020
Externally published	Yes

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@article{30f1c9b5424449e6953cf92acda35dd2,

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

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.",

author = "\{INTRuST Clinical Consortium\} and \{VA Mid-Atlantic MIRECC Workgroup\} and \{PGC PTSD Epigenetics Workgroup\} and Smith, \{Alicia K.\} and Andrew Ratanatharathorn and Maihofer, \{Adam X.\} and Naviaux, \{Robert K.\} and Aiello, \{Allison E.\} and Amstadter, \{Ananda B.\} and Ashley-Koch, \{Allison E.\} and Baker, \{Dewleen G.\} and Beckham, \{Jean C.\} and Boks, \{Marco P.\} and Evelyn Bromet and Michelle Dennis and Sandro Galea and Garrett, \{Melanie E.\} and Elbert Geuze and Guia Guffanti and Hauser, \{Michael A.\} and Seyma Katrinli and Varun Kilaru and Kessler, \{Ronald C.\} and Kimbrel, \{Nathan A.\} and Koenen, \{Karestan C.\} and Kuan, \{Pei Fen\} and Kefeng Li and Logue, \{Mark W.\} and Adriana Lori and Luft, \{Benjamin J.\} and Miller, \{Mark W.\} and Naviaux, \{Jane C.\} and Nugent, \{Nicole R.\} and Xuejun Qin and Ressler, \{Kerry J.\} and Risbrough, \{Victoria B.\} and Rutten, \{Bart P.F.\} and Stein, \{Murray B.\} and Ursano, \{Robert J.\} and Eric Vermetten and Vinkers, \{Christiaan H.\} and Lin Wang and Youssef, \{Nagy A.\} and Christine Marx and Gerry Grant and Qin, \{Xue Jun\} and Sonia Jain and McAllister, \{Thomas W.\} and Ross Zafonte and Ariel Lang and Raul Coimbra and Norberto Andaluz and Lori Shutter",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

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doi = "10.1038/s41467-020-19615-x",

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AU - INTRuST Clinical Consortium

AU - VA Mid-Atlantic MIRECC Workgroup

AU - PGC PTSD Epigenetics Workgroup

AU - Smith, Alicia K.

AU - Ratanatharathorn, Andrew

AU - Maihofer, Adam X.

AU - Naviaux, Robert K.

AU - Aiello, Allison E.

AU - Amstadter, Ananda B.

AU - Ashley-Koch, Allison E.

AU - Baker, Dewleen G.

AU - Beckham, Jean C.

AU - Boks, Marco P.

AU - Bromet, Evelyn

AU - Dennis, Michelle

AU - Galea, Sandro

AU - Garrett, Melanie E.

AU - Geuze, Elbert

AU - Guffanti, Guia

AU - Hauser, Michael A.

AU - Katrinli, Seyma

AU - Kilaru, Varun

AU - Kessler, Ronald C.

AU - Kimbrel, Nathan A.

AU - Koenen, Karestan C.

AU - Kuan, Pei Fen

AU - Li, Kefeng

AU - Logue, Mark W.

AU - Lori, Adriana

AU - Luft, Benjamin J.

AU - Miller, Mark W.

AU - Naviaux, Jane C.

AU - Nugent, Nicole R.

AU - Qin, Xuejun

AU - Ressler, Kerry J.

AU - Risbrough, Victoria B.

AU - Rutten, Bart P.F.

AU - Stein, Murray B.

AU - Ursano, Robert J.

AU - Vermetten, Eric

AU - Vinkers, Christiaan H.

AU - Wang, Lin

AU - Youssef, Nagy A.

AU - Marx, Christine

AU - Grant, Gerry

AU - Qin, Xue Jun

AU - Jain, Sonia

AU - McAllister, Thomas W.

AU - Zafonte, Ross

AU - Lang, Ariel

AU - Coimbra, Raul

AU - Andaluz, Norberto

AU - Shutter, Lori

PY - 2020/12/1

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N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85096786381

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DO - 10.1038/s41467-020-19615-x

M3 - Article

C2 - 33235198

AN - SCOPUS:85096786381

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5965

ER -

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

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