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

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 arylhydrocarbon 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.

Reference: 
Alicia K. Smith ; Andrew Ratanatharathorn , Adam X. Maihofer , Robert K. Naviaux , Allison E. Aiello , Ananda B. Amstadter , Allison E. Ashley-Koch , Dewleen G. Baker , Jean C. Beckham , Marco P. Boks , Evelyn Bromet , Michelle Dennis , Sandro Galea , Melanie E. Garrett , Elbert Geuze , Guia Guffanti , Michael A. Hauser , Seyma Katrinli , Varun Kilaru , Ronald C. Kessler , Nathan A. Kimbrel , Karestan C. Koenen , Pei-Fen Kuan , Kefeng Li , Mark W. Logue , Adriana Lori , Benjamin J. Luft , Mark W. Miller , Jane C. Naviaux , Nicole R. Nugent , Xuejun Qin , Jerry J. Ressler , Victoria B. Risbrough , Bart P. F. Rutten , Murray B. Stein , Robert J. Ursano , Eric Vermetten , Christiaan H. Vinkers , Lin Wang , Nagy A. Youssef , INTRuST Clinical Consortium, VA Mid-Atlantic MIRECC Workgroup, PGC PTSD Epigenetics Workgroup, Monica Uddin & Caroline M. Nievergelt , Christine Marx , Gerry Grant , Murray Stein , Michael A. Hauser , Xue-Jun Qin , Sonia Jain , Thomas W. McAllister , Ross Zafonte , Ariel Lang , Raul Coimbra , Norberto Andaluz , Lori Shutter & Mark S. George ; Mira Brancu , Patrick S. Calhoun , Eric Dedert , Eric B. Elbogen , John A. Fairbank , Robin A. Hurley , Jason D. Kilts , Angela Kirby , Christine E. Marx , Scott D. McDonald , Scott D. Moore , Rajendra A. Morey , Jennifer C. Naylor , Jared A. Rowland , Cindy Swinkels , Steven T. Szabo , Katherine H. Taber , Larry A. Tupler , Elizabeth E. Van Voorhees & Ruth E. Yoash-Gantz Allison E. Aiello, Ananda B. Amstadter, Allison E. Ashley-Koch , Dewleen G. Baker , Archana Basu , Jean C. Beckham , Marco P. Boks , Leslie A. Brick , Evelyn Bromet , Shareefa Dalvie , Nikolaos P. Daskalakis , Michelle Dennis , Judith B. M. Ensink , Sandro Galea , Melanie E. Garrett, Elbert Geuze , Guia Guffanti , Michael A. Hauser , Sian M. J. Hemmings , Ryan Herringa , Sylvanus Ikiyo , Seyma Katrinli , Ronald C. Kessler , Varun Kilaru , Nathan A. Kimbrel , Nastassja Koen , Karestan C. Koenen , Pei Fen Kuan , Mark W. Logue , Adriana Lori , Benjamin J. Luft , Adam X. Maihofer, Mark W. Miller , Janitza Montalvo-Ortiz , Caroline M. Nievergelt , Danny Nispeling , Nicole R. Nugent , John Pfeiffer , XueJun Qin , Andrew Ratanatharathorn , Kerry J. Ressler , Victoria B. Risbrough , Bart P. F. Rutten , Dick Schijven , Soraya Seedat , Gen Shinozaki , Alicia K. Smith , Murray B. Stein , Jennifer A. Sumner , Patricia Swart , Audrey Tyrka , Monica Uddin , Robert J. Ursano , Mirjam Van Zuiden, Eric Vermetten , Christiaan H. Vinkers & Agaz Wani , Erika J. Wolf , Nagy A. Youssef & Anthony Zannas | 2020
In: Nature Communications ; ISSN : 2041-1723 | 11 | 5965
https://doi.org/10.1038/s41467-020-19615-x
Keywords: 
Epigenetics, Genetic Markers, Genetics, Immunological Symptoms, Meta Analysis, Military Personnel, Posttraumatic Stress Disorder, Psychotrauma, PTSD (en)
Affiliation author(s): 
ARQ National Psychotrauma Centre