Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR
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Published:2020-11-24
Issue:1
Volume:11
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Smith Alicia K.ORCID, , Ratanatharathorn AndrewORCID, Maihofer Adam X.ORCID, Naviaux Robert K., Aiello Allison E., Amstadter Ananda B., Ashley-Koch Allison E.ORCID, Baker Dewleen G.ORCID, Beckham Jean C., Boks Marco P., Bromet Evelyn, Dennis Michelle, Galea SandroORCID, Garrett Melanie E., Geuze ElbertORCID, Guffanti Guia, Hauser Michael A., Katrinli SeymaORCID, Kilaru Varun, Kessler Ronald C.ORCID, Kimbrel Nathan A., Koenen Karestan C., Kuan Pei-FenORCID, Li KefengORCID, Logue Mark W., Lori Adriana, Luft Benjamin J.ORCID, Miller Mark W.ORCID, Naviaux Jane C., Nugent Nicole R., Qin XuejunORCID, Ressler Kerry J.ORCID, Risbrough Victoria B.ORCID, Rutten Bart P. F.ORCID, Stein Murray B.ORCID, Ursano Robert J.ORCID, Vermetten EricORCID, Vinkers Christiaan H.ORCID, Wang Lin, Youssef Nagy A.ORCID, Uddin Monica, Nievergelt Caroline M., ,
Abstract
AbstractEpigenetic 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.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of Mental Health U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse Nederlandse Organisatie voor Wetenschappelijk Onderzoek U.S. Department of Health & Human Services | CDC | National Institute for Occupational Safety and Health U.S. Department of Defense U.S. Department of Veterans Affairs
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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