# Validation of PTSD signals across multiple biological domains for the development of diagnostic biomarkers for PTSD in military populations to improve clinical care of Veterans

> **NIH VA I21** · VA SAN DIEGO HEALTHCARE SYSTEM · 2023 · —

## Abstract

Post-traumatic stress disorder (PTSD) is likely a systemic illness, affecting not only the brain, but
the entire body. Accordingly, efforts to identify biological signals for risk prediction and diagnosis
have been performed across multiple biological domains, including –omic assessments of genes
and epigenetic changes, and panels including a combination of biomarkers spanning multiple
systems. Large-scale genome-wide association studies by the Million Veteran Program (MVP)
and Psychiatric Genomics Consortium (PGC) have identified >20 genes associated with PTSD
diagnosis/symptoms and developed polygenic risk scores (PRS) to predict risk of developing
PTSD after exposure to a traumatic event. Adding to PRS, epigenetic mediation of environmental
influences may be a key mechanism of differential susceptibility to PTSD. The largest meta-
analysis to date using blood-derived methylation changes prior to and following combat exposure
in military cohorts identified several epigenome-wide significant CpGs and differentiated regions.
Finally, a recent study aiming at multi-omic biomarker identification for diagnosing warzone-
related PTSD has developed a multi-omic diagnostic panel which integrates protein, metabolite,
miRNA, methylation and hormone data to predict PTSD diagnosis. Although well powered and
developed from unbiased discovery approaches, these biomarkers for PTSD are still preliminary
and await systematic validation across specific patient populations such as Veterans seeking care
for PTSD at the VA. If the PRS, epigenomic signature, and peripheral biomarker panel are not
replicated in treatment-seeking Veterans with PTSD, translating these putative biomarkers from
academic investigations to eventual clinical utility for Veteran care will be unlikely. The VA
recognizes this need and developed the RFA BX 21-043 which seeks to fund proposals to
“validate clinically significant findings such as identification of a therapeutic target or novel
biomarker panel based on phenotypic and “omic” data acquired from population studies, …
including genetic risk factors, pathophysiological pathways, treatment target identification and
biomarker discovery.” The goal of this proposal is to validate the PRS, methylation signature and
multi-omic panel in independent cohorts with existing, longitudinal samples collected from
treatment-seeking Veterans. Results of these studies will be highly informative for development
of these biomarkers for precision medicine applications.

## Key facts

- **NIH application ID:** 10617231
- **Project number:** 5I21BX005872-02
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Victoria B Risbrough
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-04-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10617231

## Citation

> US National Institutes of Health, RePORTER application 10617231, Validation of PTSD signals across multiple biological domains for the development of diagnostic biomarkers for PTSD in military populations to improve clinical care of Veterans (5I21BX005872-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10617231. Licensed CC0.

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