# Gene-Environment Interactions in the Vascular Endothelium

> **NIH NIH F30** · WAYNE STATE UNIVERSITY · 2021 · $43,636

## Abstract

Abstract: Gene‐Environment Interactions in the Vascular Endothelium
 Genome‐wide association studies (GWAS) have identified thousands of genetic variants associated with complex
traits. However, only a limited number of environmental factors are measured in GWAS. Thus, some of the genetic effect
sizes measured may be underestimated when the underlying environment is composed of many exposures. Controlling
for, or accurately measuring, all possible environmental factors in a GWAS setting is a formidable challenge. Instead,
molecular phenotypes (gene expression, chromatin accessibility) measured in tightly controlled cellular environments
provide a more tractable setting in which to study gene‐environment interactions (GxE) in the absence of other
confounding variables.
 In this proposed research, I will develop methods to investigate causes and consequences of GxE, and I will apply
them to analyze the vascular endothelium at the molecular, interindividual, and phenotypic levels. I will use data we have
already collected from human umbilical vein endothelial cells (HUVECs) from 17 healthy donors, for 3 treatment conditions
(dexamethasone, retinoic acid, and caffeine) and appropriate vehicle‐controls. We genotyped and performed RNA‐seq
and ATAC‐seq to model genetic and environmental effects on gene regulation and chromatin accessibility in the vascular
endothelium, a common site of pathology in cardiovascular disease (e.g., atherosclerosis).
 I will first identify transcription factors (TFs) which regulate response to each treatment and predict regulatory
variants which affect gene expression in response to treatment. I will then develop a joint allele‐specific expression (ASE)
and quantitative trait loci (QTL) mapping approach to experimentally identify GxE‐QTLs in our dataset and validate the
computational predictions of the effects of regulatory variants. These variants will be used to fine map and functionally
annotate GWAS SNPs associated with cardiovascular disease. Ultimately, findings discovered here will provide insights
into the mechanisms for GxE in cardiovascular disease, and the developed methods will be broadly applicable to the study
of GxE in other cell types and environmental conditions.

## Key facts

- **NIH application ID:** 10077210
- **Project number:** 5F30GM131580-03
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Anthony Scott Findley
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $43,636
- **Award type:** 5
- **Project period:** 2018-12-31 → 2022-12-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077210

## Citation

> US National Institutes of Health, RePORTER application 10077210, Gene-Environment Interactions in the Vascular Endothelium (5F30GM131580-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10077210. Licensed CC0.

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