Epigenome-Wide Meta-Analysis of PTSD across 10 Military and Civilian Cohorts Identifies Methylation Changes in AHRR

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Citation

Smith, Alicia K.; Ratanatharathorn, Andrew; Maihofer, Adam X.; Naviaux, Robert K.; Aiello, Allison E.; Amstadter, Ananda B.; Ashley-Koch, Allison E.; Baker, Dewleen G.; Beckham, Jean C.; & Boks, Marco P., et al. (2020). Epigenome-Wide Meta-Analysis of PTSD across 10 Military and Civilian Cohorts Identifies Methylation Changes in AHRR. Nature Communications, 11(1), 5965. PMCID: PMC7686485

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.

URL

http://dx.doi.org/10.1038/s41467-020-19615-x

Reference Type

Journal Article

Year Published

2020

Journal Title

Nature Communications

Author(s)

Smith, Alicia K.
Ratanatharathorn, Andrew
Maihofer, Adam X.
Naviaux, Robert K.
Aiello, Allison E.
Amstadter, Ananda B.
Ashley-Koch, Allison E.
Baker, Dewleen G.
Beckham, Jean C.
Boks, Marco P.
Bromet, Evelyn J.
Dennis, Michelle
Galea, Sandro
Garrett, Melanie E.
Geuze, Elbert
Guffanti, Guia
Hauser, Michael A.
Katrinli, Seyma
Kilaru, Varun
Kessler, Ronald C.
Kimbrel, Nathan A.
Koenen, Karestan C.
Kuan, Pei-Fen
Li, Kefeng
Logue, Mark W.
Lori, Adriana
Luft, Benjamin J.
Miller, Mark W.
Naviaux, Jane C.
Nugent, Nicole R.
Qin, Xuejun
Ressler, Kerry J.
Risbrough, Victoria B.
Rutten, Bart P. F.
Stein, Murray B.
Ursano, Robert J.
Vermetten, Eric
Vinkers, Christiaan H.
Wang, Lin
Youssef, Nagy A.
INTRuST Clinical Consortium,
VA Mid-Atlantic MIRECC Workgroup,
PGC PTSD Epigenetics Workgroup,
Uddin, Monica
Nievergelt, Caroline M.

Article Type

Regular

PMCID

PMC7686485

Data Set/Study

Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup

Continent/Country

United States of America

State

Nonspecific

ORCiD

Aiello - 0000-0001-7029-2537