# Modeling gene x environment interactions in post-traumatic stress disorder.

> **NIH NIH F30** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $51,694

## Abstract

PROJECT SUMMARY
Posttraumatic stress disorder (PTSD) is a common, debilitating disorder, triggered by exposure to a traumatic
event. PTSD is often under-diagnosed and undertreated, despite early detection and treatment governing
favorable outcomes. Better identification of elements of disorder susceptibility or resilience is important for
prompt delivery of care to mitigate disorder burden. As PTSD has shown to be heritable, a prevailing theory of
disorder susceptibility is genetic. Large-scale genome wide association studies (GWAS) have revealed an
estimated single-nucleotide polymorphism (SNP)-based heritability of 5-20%. Yet, environmental factors, such
as childhood trauma, have also shown to independently predict PTSD development. Genome-wide integration
of PTSD-associated genetic loci with stressful exposures may elucidate gene by environment interactions that
influence disorder susceptibility. In this proposal, I will investigate loci with joint genetic and environmental
contributions to PTSD risk, employing an integrative multi-level approach to examine and validate brain region
and cell type-specific regulation. One major issue integrating GWAS findings with environmental exposures is
the largely non-coding nature of GWAS-identified loci, obscuring clear functional ramifications. To overcome this,
I will associate identified variants with nearby expression changes to uncover regulation of proximal or distal
gene targets. Such variants with transcriptomic regulatory activity are termed expression quantitative trait loci
(eQTLs). As transcriptomic regulation is context-dependent, eQTLs capture genetically and environmentally
regulated expression, making them useful for deciphering genomic regulation of PTSD. I performed a preliminary
eQTL search in post-mortem brain samples from the dorsolateral pre-frontal cortex (DLPFC), demonstrating that
stress-interactive eQTLs are detectable in brains of trauma-exposed cohorts. In Aim 1, I will extend this analysis
beyond the DLPFC to the medial amygdala, to uncover the regulatory landscape of genetic stress response
across the brain. In Aim 2, I will examine causality of these variants to demonstrate stress-dependent regulation.
I have developed an in vitro model capturing PTSD-specific stress response. In this model, candidate effector
variants will be interrogated for downstream effects impacting disorder biology. This will be accomplished via
training in large scale CRISPR-screening methods and in computational probing of convergent downstream
pathways. This work will take place within the Icahn School of Medicine at Mount Sinai (ISMMS) and Yale
University, currently ranked #11 and #10 among the nation’s best medical schools for research, respectively.
Between the Departments of Genetics and Neuroscience, I am supported by over 100,000 ft2 of research
programs and 4500 ft2 of institutional core facilities, in addition to over $200 million in scientific computing
resources. Together, this fellowshi...

## Key facts

- **NIH application ID:** 10878745
- **Project number:** 5F30MH132324-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Carina Seah
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $51,694
- **Award type:** 5
- **Project period:** 2023-06-26 → 2027-06-25

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878745

## Citation

> US National Institutes of Health, RePORTER application 10878745, Modeling gene x environment interactions in post-traumatic stress disorder. (5F30MH132324-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10878745. Licensed CC0.

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