# Genetic and Epigenetic Biomarkers of PTSD

> **NIH VA I01** · VA BOSTON HEALTH CARE SYSTEM · 2020 · —

## Abstract

Posttraumatic stress disorder (PTSD) is a serious mental disorder that occurs in response to a
traumatic event. In this project, we will examine DNA methylation, an epigenetic form of gene regulation, for
association with PTSD. We will utilize data from state of the art methylation beadchips that measure more than
850,000 locations along the genome. First, we will perform an epigenome-wide association study (EWAS) of
PTSD in blood. This will be followed by a candidate gene analysis of PTSD and glucocorticoid-responsive
genes based on our recent genome-wide gene expression study of PTSD (Logue et al., 2015). That study
found genes whose expression in blood was closely correlated with PTSD case/control status, including many
glucocorticoid-responsive genes that have not been previously studied in relationship to PTSD. These
analyses will utilize data from two U.S. Department of Veterans Affairs (VA) cohorts (total n>1000) made up
primarily of US veterans with a high prevalence of PTSD. Replication of these findings will be sought from a
large epigenetics consortium. Then, we will perform genome-wide and candidate-gene association studies of
PTSD using tissue from 50 brains obtained from a recently formed PTSD brain bank. We will specifically
analyze methylation in the hippocampus, amygdala, and hypothalamus—three regions implicated in PTSD,
HPA axis functioning, and anxiety. The impact of PTSD-associated differential methylation on gene expression
in the brain will be investigated using chromogenic in-situ hybridization that will provide a measure of gene
expression as well as provide localization of that expression to particular cell types (e.g. neurons or glia). We
will investigate the effects of these differences on neural integrity using a VA cohort with existing MRI data
(n>400). In this way, we will link PTSD-associated DNA methylation differences in blood to DNA methylation
differences in the brain, gene-expression differences in the brain, and morphological differences in the brain.
This will yield clinically relevant biomarkers for PTSD, trauma exposure, and PTSD-related symptomatology
and important information about the biology underpinning the observed associations.

## Key facts

- **NIH application ID:** 9859309
- **Project number:** 5I01BX003477-04
- **Recipient organization:** VA BOSTON HEALTH CARE SYSTEM
- **Principal Investigator:** MARK W LOGUE
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-01-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859309

## Citation

> US National Institutes of Health, RePORTER application 9859309, Genetic and Epigenetic Biomarkers of PTSD (5I01BX003477-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9859309. Licensed CC0.

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