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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Smith, AK; Ratanatharathorn, A; Maihofer, AX; Naviaux, RK; Aiello, AE; Amstadter, AB; Ashley-Koch, AE; Baker, DG; Beckham, JC; Boks, MP; Bromet, E; Dennis, M; Galea, S; Garrett, ME; Geuze, E; Guffanti, G; Hauser, MA; Katrinli, S; Kilaru, V; Kessler, RC; Kimbrel, NA; Koenen, KC; Kuan, P-F; Li, K; Logue, MW; Lori, A; Luft, BJ; Miller, MW; Naviaux, JC; Nugent, NR; Qin, X; Ressler, KJ; Risbrough, VB; Rutten, BPF; Stein, MB; Ursano, RJ; Vermetten, E; Vinkers, CH; Wang, L; Youssef, NA; INTRuST Clinical Consortium, ; VA Mid-Atlantic MIRECC Workgroup, ; PGC PTSD Epigenetics Workgroup, ; Uddin, M; Nievergelt, CM

Published Date

  • November 24, 2020

Published In

Volume / Issue

  • 11 / 1

Start / End Page

  • 5965 -

PubMed ID

  • 33235198

Pubmed Central ID

  • PMC7686485

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-020-19615-x

Language

  • eng

Conference Location

  • England