TY - JOUR
T1 - Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR
AU - INTRuST Clinical Consortium
AU - VA Mid-Atlantic MIRECC Workgroup
AU - PGC PTSD Epigenetics Workgroup
AU - Smith, Alicia K.
AU - Ratanatharathorn, Andrew
AU - Maihofer, Adam X.
AU - Naviaux, Robert K.
AU - Aiello, Allison E.
AU - Amstadter, Ananda B.
AU - Ashley-Koch, Allison E.
AU - Baker, Dewleen G.
AU - Beckham, Jean C.
AU - Boks, Marco P.
AU - Bromet, Evelyn
AU - Dennis, Michelle
AU - Galea, Sandro
AU - Garrett, Melanie E.
AU - Geuze, Elbert
AU - Guffanti, Guia
AU - Hauser, Michael A.
AU - Katrinli, Seyma
AU - Kilaru, Varun
AU - Kessler, Ronald C.
AU - Kimbrel, Nathan A.
AU - Koenen, Karestan C.
AU - Kuan, Pei Fen
AU - Li, Kefeng
AU - Logue, Mark W.
AU - Lori, Adriana
AU - Luft, Benjamin J.
AU - Miller, Mark W.
AU - Naviaux, Jane C.
AU - Nugent, Nicole R.
AU - Qin, Xuejun
AU - Ressler, Kerry J.
AU - Risbrough, Victoria B.
AU - Rutten, Bart P.F.
AU - Stein, Murray B.
AU - Ursano, Robert J.
AU - Vermetten, Eric
AU - Vinkers, Christiaan H.
AU - Wang, Lin
AU - Youssef, Nagy A.
AU - Marx, Christine
AU - Grant, Gerry
AU - Stein, Murray
AU - Qin, Xue Jun
AU - Jain, Sonia
AU - McAllister, Thomas W.
AU - Zafonte, Ross
AU - Lang, Ariel
AU - Coimbra, Raul
AU - Andaluz, Norberto
AU - Ensink, Judith B. M.
AU - van Zuiden, Mirjam
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85096786381&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-020-19615-x
DO - https://doi.org/10.1038/s41467-020-19615-x
M3 - Article
C2 - 33235198
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5965
ER -