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


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.

SUBMITTER: Smith AK 

PROVIDER: S-EPMC7686485 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Smith Alicia K AK   Ratanatharathorn Andrew A   Maihofer Adam X AX   Naviaux Robert K RK   Aiello Allison E AE   Amstadter Ananda B AB   Ashley-Koch Allison E AE   Baker Dewleen G DG   Beckham Jean C JC   Boks Marco P MP   Bromet Evelyn E   Dennis Michelle M   Galea Sandro S   Garrett Melanie E ME   Geuze Elbert E   Guffanti Guia G   Hauser Michael A MA   Katrinli Seyma S   Kilaru Varun V   Kessler Ronald C RC   Kimbrel Nathan A NA   Koenen Karestan C KC   Kuan Pei-Fen PF   Li Kefeng K   Logue Mark W MW   Lori Adriana A   Luft Benjamin J BJ   Miller Mark W MW   Naviaux Jane C JC   Nugent Nicole R NR   Qin Xuejun X   Ressler Kerry J KJ   Risbrough Victoria B VB   Rutten Bart P F BPF   Stein Murray B MB   Ursano Robert J RJ   Vermetten Eric E   Vinkers Christiaan H CH   Wang Lin L   Youssef Nagy A NA   Uddin Monica M   Nievergelt Caroline M CM  

Nature communications 20201124 1


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 relativ  ...[more]

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