It is not clear why some people develop posttraumatic stress disorder (PTSD) in response to a traumatic event. DNA methylation, an epigenetic mark that associates with trauma and other environmental exposures, predicts PTSD in multiple studies, and methylation of some genes may be informative for early prediction and treatment of PTSD. The purpose of this study is to facilitate an epigenome-wide association study (EWAS) of PTSD in participating cohorts in Psychiatric Genomics Consortium (PGC) PTSD workgroup. In this study, we will leverage thousands of cross-sectional and longitudinal samples of PTSD cases and trauma-exposed controls with methylome data collected using the same genome-wide array. The meta-analyses of these samples will be allow for identification of DNA methylation patterns that predict PTSD in diverse subjects as well as those that are sex-specific or specific to type of trauma (child vs. adult or combat vs. civilian). DNA methylation patterns that are most predictive of PTSD will be replicated in an independent cohort of cases and controls. The results of this study provide insight into the biologic pathways underlying the development and progression of PTSD, will complement ongoing efforts to identify therapeutic targets for PTSD, and will inform prospective studies of PTSD and trauma exposure that are underway.

Public Health Relevance

Recent studies report DNA methylation differences that distinguish PTSD cases from controls. The purpose of this application is to facilitate a multi-site epigenome-wide analysis of PTSD, with the long-term goal of developing an epigenetic panel that informs the prediction or treatment of PTSD.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Behavioral Genetics and Epidemiology Study Section (BGES)
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Koester, Susan E
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Emory University
Schools of Medicine
United States
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Nievergelt, Caroline M; Ashley-Koch, Allison E; Dalvie, Shareefa et al. (2018) Genomic Approaches to Posttraumatic Stress Disorder: The Psychiatric Genomic Consortium Initiative. Biol Psychiatry 83:831-839
Wolf, Erika J; Maniates, Hannah; Nugent, Nicole et al. (2018) Traumatic stress and accelerated DNA methylation age: A meta-analysis. Psychoneuroendocrinology 92:123-134
Pfeiffer, John R; Mutesa, Leon; Uddin, Monica (2018) Traumatic Stress Epigenetics. Curr Behav Neurosci Rep 5:81-93
Maddox, S A; Kilaru, V; Shin, J et al. (2018) Estrogen-dependent association of HDAC4 with fear in female mice and women with PTSD. Mol Psychiatry 23:658-665
Logue, Mark W; Smith, Alicia K; Wolf, Erika J et al. (2017) The correlation of methylation levels measured using Illumina 450K and EPIC BeadChips in blood samples. Epigenomics 9:1363-1371
Ratanatharathorn, Andrew; Boks, Marco P; Maihofer, Adam X et al. (2017) Epigenome-wide association of PTSD from heterogeneous cohorts with a common multi-site analysis pipeline. Am J Med Genet B Neuropsychiatr Genet 174:619-630