Epigenome-wide association studies identify novel DNA methylation sites associated with PTSD: a meta-analysis of 23 military and civilian cohorts

作者：Şeyma Katrinli, Agaz H. Wani, Adam X. Maihofer, Andrew Ratanatharathorn, Nikolaos P. Daskalakis, Janitza L. 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 J. Bromet, Frances A. Champagne, Chia‐Yen Chen, Shareefa Dalvie, Michelle F. Dennis, Segun Fatumo, Catherine Fortier, Sandro Galea, Melanie E. Garrett, Elbert Geuze, Gerald A. Grant, Michael A. Hauser, Jasmeet P. Hayes, Sian 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, Léon Mutesa, Charles B. Nemeroff, Nicole R. Nugent, Holly K. Orcutt, Xuejun 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 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, Reid S. Alisch, Ananda B. Amstadter, Don Armstrong, Archana Basu, Nicole L. Bjorklund, Barbara H. Chaiyachati, Judith Ensink, Leland L. Fleming, Joel Gelernter, Ryan J. Herringa, Sonia Jain, Diana L. Juvinao-Quintero, Elizabeth Ketema, José Jaime Martínez‐Magaña, Burook Misganaw, Shiela Tiemi Nagamatsu, Danny Nispeling, John R. Pfeiffer, Christian Schmahl, Gen Shinozaki, Clara Snijders, Jennifer A. Sumner, Patricia Swart, Audrey R. Tyrka, Mirjam van Zuiden, Womersley, Nagy A. Youssef, Yuanchao Zheng, Yiwen Zhu, Lea Zillich, PsychENCODE PTSD BrainOmics Project, Dhivya Arasappan, Sabina Berretta, Rahul Bharadwaj, Leonardo Collado‐Torres, Christos Chatzinakos, Chris P. DiPietro, Duc M. Duong, Amy Deep‐Soboslay, Nick Eagles, Louise A. Huuki-Myers, Thomas M. Hyde, Artemis Iatrou, Geo Pertea, Deanna Ross, Nicholas T. Seyfried, Joo Heon Shin, Victor E. Alvarez, David M. Benedek, Alicia Che, Dianne A. Cruz, David A. Davis, Matthew J. Girgenti, Ellen J. Hoffman, Paul E. Holtzheimer, Alfred P. Kaye, John H. Krystal, Adam Labadorf, Terence M. Keane, Ann C. McKee, Brian P. Marx, Crystal M. Noller, Meghan E. Pierce, William K. Scott, Paula P. Schnurr, Krista D. DiSano, Thor D. Stein, Douglas E. Williamson, Keith A. Young, Monica Uddin, Caroline M. Nievergelt, Alicia K. Smith, Mark W. Logue · 发表于：Genome Medicine · 年份：2024 · DOI：10.1186/s13073-024-01417-1 · 被引用次数：24 · 研究领域：Epigenetics and DNA Methylation、Mental Health via Writing、Genetic Associations and Epidemiology

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,...