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


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


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.


Reference Type

Journal Article

Article Type


Year Published


Journal Title

Nature Communications


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.



Data Set/Study

Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup


United States of America