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

Smith, A.K.; Ratanatharathorn, A.; Maihofer, A.X.; Naviaux, R.K.; Aiello, A.E.; Amstadter, A.B.; Ashley-Koch, A.E.; Baker, D.G.; Beckham, J.C.; Boks, M.P.; Bromet, E.; Dennis, M.; Galea, S.; Garrett, M.E.; Geuze, E.; Guffanti, G.; Hauser, M.A.; Katrinli, S.; Kilaru, V.; Kessler, R.C.; Kimbrel, N.A.; Koenen, K.C.; Kuan, P.F.; Li, K.F.; Logue, M.W.; Lori, A.; Luft, B.J.; Miller, M.W.; Naviaux, J.C.; Nugent, N.R.; Qin, X.J.; Ressler, K.J.; Risbrough, V.B.; Rutten, B.P.F.; Stein, M.B.; Ursano, R.J.; Vermetten, E.; Vinkers, C.H.; Wang, L.; Youssef, N.A.; Uddin, M.; Nievergelt, C.M.; INTRuST Clinical Consortium; VA Mid-Atlantic MIRECC Workgrp; PGC PTSD Epigenetics Workgrp

doi:doi:10.1038/s41467-020-19615-x

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....Show moreEpigenetic 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. PTSD has been associated with DNA methylation of specific loci in the genome, but studies have been limited by small sample sizes. Here, the authors perform a meta-analysis of DNA methylation data from 10 different cohorts and identify CpGs in AHRR that are associated with PTSD.Show less

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