# Genomics of PTSD and Related Traits

> **NIH VA I01** · VA CONNECTICUT HEALTHCARE SYSTEM · 2024 · —

## Abstract

Abstract
Posttraumatic stress disorder (PTSD) is a major problem among military veterans and civilians alike, yet
despite ongoing improvements in our understanding, its pathophysiology requires further intensive
investigation. The Veterans Affairs (VA) Million Veteran Program (MVP) is an ideal setting for study of this
problem, and we have led first a highly productive Cooperative Studies Program project (CSP#575B) in the
MVP context to identify genetic risk factors relevant to PTSD and related traits; then, the first iteration of our
MERIT project (MVP025), for which this is a competing renewal. From our prior work, we published PTSD
genetics data in multiple high-impact journals; and other products of the project relating to anxiety, depression,
alcohol use, and other traits. Over the course of the research, we assembled an expert team well-qualified to
continue productively. To continue and extend this work, we propose analyses of PTSD and related traits in the
growing MVP sample, including epigenetics and whole genome sequence (WGS) data, considering additional
kinds of genetic variation, and more extensive post-GWAS analysis. Some of our key findings have concerned
the relationship of PTSD to other psychiatric and medical disorders, for example, cardiovascular disease – we
will expand upon this work also. Other work pertaining to PTSD (e.g. study of resilience traits, individual PCL-
17 item phenotypes, and sex-specific analyses) is underway. We will continue to explore PTSD subtypes and
individual signs and symptoms from a genetic perspective. Discerning subtypes will be critical for the
advancement of precision treatment of PTSD: genetic subtype may predict treatment response.
With more MVP subjects there will be increased power to map relevant traits. We will continue GWAS of traits
related to PTSD in the expanded sample. There is very high comorbidity of PTSD with substance use disorder
traits; we propose to explore substance use-related traits as well, including alcohol, opioid, nicotine,
stimulants, and other substances. We will also study additional traits phenotypically associated with PTSD,
such as cognitive decline, Alzheimer’s disease, persistent post-concussive symptoms, and other traits with
higher or lower risk or differing course in PTSD subjects than in the general population. We will investigate
polygenic overlap between PTSD and related traits. We will use approaches that permit testing of causality
among these correlated traits (e.g., Mendelian Randomization) and that can help establish the genetic
relationships between sets of traits, such as genomic structural equation modeling. We will apply methods
such as MiXeR to identify unique and shared polygenic components.
To maximize the scientific value of these data we will undertake meta-analyses and replicate our findings in
collaboration with other EHR-linked biobank consortia and collaborate with and share data with the Psychiatric
Genomics Consortium (PGC) PTSD Workgroup...

## Key facts

- **NIH application ID:** 10805895
- **Project number:** 2I01BX006482-05
- **Recipient organization:** VA CONNECTICUT HEALTHCARE SYSTEM
- **Principal Investigator:** JOEL GELERNTER
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2019-07-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10805895

## Citation

> US National Institutes of Health, RePORTER application 10805895, Genomics of PTSD and Related Traits (2I01BX006482-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10805895. Licensed CC0.

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