# Genomics of PTSD and Related Traits

> **NIH VA I01** · VA CONNECTICUT HEALTHCARE SYSTEM · 2022 · —

## Abstract

ABSTRACT
 Posttraumatic stress disorder (PTSD) is a major problem among military Veterans, yet
its pathophysiology is poorly understood. The Veterans Affairs (VA) Million Veteran Program
(MVP) is an ideal setting for study of this problem, and we are completing a Cooperative Studies
Program project (CSP#575B), in the MVP context, to identify genetic risk factors relevant to
PTSD and related traits. Our CSP-MVP Alpha Project for the Genomics of PTSD has been
highly successful at mapping gene loci, so far for PTSD re-experiencing and other related
phenotypes (such as “maximum habitual alcohol use”). Although PTSD GWAS data per se are
under analysis, considerable work still needs to be done to fully develop and maximize the
scientific value of the MVP for PTSD and related phenotypes, as the analyzable MVP sample
continues to grow. Over the course of this project, we have assembled an expert team well-
qualified to continue the work. To continue this work, we propose a set of extended analyses in
a larger sample, and post-GWAS analyses.
 With more subjects there will be increased power to map relevant traits; we will continue
GWAS of PTSD and related traits in the expanded sample. There is very high comorbidity of
PTSD with substance use disorder traits; we propose to explore SUDs as well, including alcohol
dependence, opioid dependence, nicotine dependence, and other SUDs.
 We will investigate single-gene and polygenic overlap between PTSD and related traits.
We will study traits phenotypically associated with PTSD, such as cognitive decline, Alzheimer’s
disease, persistent post-concussive symptoms, and immune-related disorders (such as Crohn’s
disease, rheumatoid arthritis, and multiple sclerosis) in the MVP sample. We will use
approaches that permit testing of causality among these correlated traits (e.g., Mendelian
Randomization, MR). We will complete a phenomewide association study (PheWAS) of PTSD
top GWAS-identified genes (e.g., CRHR1 and others), PTSD polygenic risk score (PRS)
analysis within MVP, and MR to detect causal mechanisms related to PTSD pathogenesis.
 With the aim of maximizing the scientific value of these data and sharing them with the
scientific community, we will also explore the possibility of replication of our findings in
collaboration with other EHR-linked biobank consortia such as the Psych-EMERGE network;
and the Psychiatric Genomics Consortium PTSD group (in which we participate presently).
 Finally, the MVP sample is suitable for advancing work in many populations that are
generally understudied. We will investigate psychiatric trait-relevant population genetics of AAs,
Latinos, East Asians, and South Asians, and other populations in the MVP system, and we will
work to maximize information from, and identify results relevant to, all populations.

## Key facts

- **NIH application ID:** 10496548
- **Project number:** 5I01CX001849-04
- **Recipient organization:** VA CONNECTICUT HEALTHCARE SYSTEM
- **Principal Investigator:** JOEL GELERNTER
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-07-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10496548

## Citation

> US National Institutes of Health, RePORTER application 10496548, Genomics of PTSD and Related Traits (5I01CX001849-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10496548. Licensed CC0.

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