1. Epigenome-wide association studies identify novel DNA methylation sites associated with PTSD: a meta-analysis of 23 military and civilian cohorts
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Seyma Katrinli, Agaz H. Wani, Adam X. Maihofer, Andrew Ratanatharathorn, Nikolaos P. Daskalakis, Janitza Montalvo-Ortiz, Diana L. Núñez-Ríos, Anthony S. Zannas, Xiang Zhao, Allison E. Aiello, Allison E. Ashley-Koch, Diana Avetyan, Dewleen G. Baker, Jean C. Beckham, Marco P. Boks, Leslie A. Brick, Evelyn Bromet, Frances A. Champagne, Chia-Yen Chen, Shareefa Dalvie, Michelle F. Dennis, Segun Fatumo, Catherine Fortier, Sandro Galea, Melanie E. Garrett, Elbert Geuze, Gerald Grant, Michael A. Hauser, Jasmeet P. Hayes, Sian M. J. Hemmings, Bertrand Russel Huber, Aarti Jajoo, Stefan Jansen, Ronald C. Kessler, Nathan A. Kimbrel, Anthony P. King, Joel E. Kleinman, Nastassja Koen, Karestan C. Koenen, Pei-Fen Kuan, Israel Liberzon, Sarah D. Linnstaedt, Adriana Lori, Benjamin J. Luft, Jurjen J. Luykx, Christine E. Marx, Samuel A. McLean, Divya Mehta, William Milberg, Mark W. Miller, Mary S. Mufford, Clarisse Musanabaganwa, Jean Mutabaruka, Leon Mutesa, Charles B. Nemeroff, Nicole R. Nugent, Holly K. Orcutt, Xue-Jun Qin, Sheila A. M. Rauch, Kerry J. Ressler, Victoria B. Risbrough, Eugène Rutembesa, Bart P. F. Rutten, Soraya Seedat, Dan J. Stein, Murray B. Stein, Sylvanus Toikumo, Robert J. Ursano, Annette Uwineza, Mieke H. Verfaellie, Eric Vermetten, Christiaan H. Vinkers, Erin B. Ware, Derek E. Wildman, Erika J. Wolf, Ross McD Young, Ying Zhao, Leigh L. van den Heuvel, PGC-PTSD Epigenetics Workgroup, PsychENCODE PTSD Brainomics Project, Traumatic Stress Brain Research Group, Monica Uddin, Caroline M. Nievergelt, Alicia K. Smith, and Mark W. Logue
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PTSD ,Trauma ,DNA methylation ,Postmortem brain ,GWAS ,Gene expression ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at multiple CpG loci across the genome. Moreover, these effects can be shared or specific to both central and peripheral tissues. Here, we aim to identify blood DNAm differences associated with PTSD and characterize the underlying biological mechanisms by examining the extent to which they mirror associations across multiple brain regions. Methods As the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup, we conducted the largest cross-sectional meta-analysis of epigenome-wide association studies (EWASs) of PTSD to date, involving 5077 participants (2156 PTSD cases and 2921 trauma-exposed controls) from 23 civilian and military studies. PTSD diagnosis assessments were harmonized following the standardized guidelines established by the PGC-PTSD Workgroup. DNAm was assayed from blood using Illumina HumanMethylation450 or MethylationEPIC (850 K) BeadChips. Within each cohort, DNA methylation was regressed on PTSD, sex (if applicable), age, blood cell proportions, and ancestry. An inverse variance-weighted meta-analysis was performed. We conducted replication analyses in tissue from multiple brain regions, neuronal nuclei, and a cellular model of prolonged stress. Results We identified 11 CpG sites associated with PTSD in the overall meta-analysis (1.44e − 09
- Published
- 2024
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