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

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 PF, 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. Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR. Nature communications. 2020 Nov 24; 11(1):5965.

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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.




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