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

2020; Nature Portfolio; Volume: 11; Issue: 1 Linguagem: Inglês

10.1038/s41467-020-19615-x

2041-1723

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 J. Bromet, Michelle F. Dennis, Sandro Galea, Melanie E. Garrett, Elbert Geuze, Guia Guffanti, Michael A. Hauser, Şeyma 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, Kerry 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, Christine E. Marx, Gerry Grant, Murray B. Stein, Xuejun Qin, Sonia Jain, Thomas W. McAllister, Ross Zafonte, Ariel J. Lang, Raúl Coimbra, Norberto Andaluz, Lori Shutter, Mark S. George, Mira Brancu, Patrick S. Calhoun, Eric A. Dedert, Eric B. Elbogen, John A. Fairbank, Robin A. Hurley, Jason D. Kilts, Angela C. 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, Archana Basu, Leslie A. Brick, Shareefa Dalvie, Nikolaos P. Daskalakis, Judith B. M. Ensink, Sian Hemmings, Ryan J. Herringa, Sylvanus Ikiyo, Nastassja Koen, Pei Fen Kuan, Janitza L. Montalvo‐Ortiz, Danny Nispeling, John R. Pfeiffer, Xuejun Qin, Kerry J. Ressler, Dick Schijven, Soraya Seedat, Gen Shinozaki, Jennifer A. Sumner, Patricia Swart, Audrey R. Tyrka, Mirjam van Zuiden, Agaz H. Wani, Erika J. Wolf, Anthony S. Zannas, Monica Uddin, Caroline M. Nievergelt,

Posttraumatic Stress Disorder Research

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.