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, associates with PTSD in multiple studies, and DNA methylation of some genes may be informative for early prediction and treatment of PTSD. Over the last 3 years, the Epigenetics Workgroup of the Psychiatric Genomics Consortium for PTSD (PGC-PTSD) has brought together data from 10 studies, with over 90 investigators from 10 countries to facilitate meta-analyses of DNA methylation (DNAm) data from cross- sectional and longitudinal studies of PTSD in civilian and military cohorts. In this renewal proposal, we will build on this highly productive collaboration by replicating our findings in an independent meta-analysis and performing the largest epigenome-wide association study (EWAS) to date in >4,700 subjects, characterizing PTSD-associated CpGs in postmortem brain tissue, identifying methylation quantitative trait loci (meQTLs) in blood and brain relevant to PTSD, and characterizing DNAm changes over the course of PTSD treatment. We are poised to rapidly and efficiently identify epigenetic markers informative for early prediction and treatment and to provide context to genetic variants that predict risk and resilience following traumatic events. This study, which aligns with ongoing PGC-PTSD efforts, will inform critical questions in the field related to the role of blood-based methylation patterns as clinically-informative biomarkers and the degree to which they reflect epigentic patterns in the brain; it will also provide insight into the biologic pathways underlying PTSD, complement ongoing efforts to identify therapeutic targets, and inform prospective studies of PTSD and trauma exposure that are underway.

Public Health Relevance

Multiple studies report DNA methylation differences that distinguish PTSD cases from symptom-free controls after exposure to a traumatic event. The purpose of this study is to identify replicable patterns of DNA methylation that associate with PTSD, characterize cross-tissue similarities between blood and brain, and determine the degree to which these patterns change in response to effective PTSD treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH108826-05A1
Application #
10072239
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Koester, Susan E
Project Start
2016-08-18
Project End
2025-05-31
Budget Start
2020-08-21
Budget End
2021-05-31
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Emory University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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Wolf, Erika J; Maniates, Hannah; Nugent, Nicole et al. (2018) Traumatic stress and accelerated DNA methylation age: A meta-analysis. Psychoneuroendocrinology 92:123-134
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