# Project 3 - Shah

> **NIH NIH P01** · DUKE UNIVERSITY · 2020 · $393,185

## Abstract

PROJECT 3 - Molecular mechanisms of gene x stress effects on pre-disease
endophenotypes
PROJECT SUMMARY
In our prior collaborative work, using a focused genetic approach in well-phenotyped human
cohorts, we have identified consistent associations between variants in candidate genes,
“endophenotypes”, and disease endpoints. However, the pathways and mechanisms mediating
our other identified genetic associations are poorly understood. Evolving molecular technologies
now enable rapid, high-throughput profiling of millions of circulating genetic and other ‘omic’
markers; using sophisticated analytic and bioinformatics techniques, these ‘omic’ profiles can be
integrated to understand biological pathways underlying disease traits, focused genetic
associations, response to medications/environment, etc. Thus, in this proposal, we will integrate
genetics, metabolomics, transcriptomics, and epigenetics profiled in blood samples from several
large, well-phenotyped cohorts to identify novel biomarkers and molecular pathways mediating
these relationships. We will also use this approach in a hypothesis generating approach for
unique phenotypes that link psychosocial stress with CVD (i.e. Takosubo’s cardiomyopathy and
mental stress induced ischemia). We will accomplish our goals for this Project through the
following Specific Aims: (1) to test the hypothesis that epigenetic variation in candidate genes
from our prior work, will also be associated with the same endophenotypes and disease
endpoints, and incrementally influence expression of the gene on those phenotypes; (2) to
integrate epigenetics, transcriptomics and metabolomics in an “unbiased” systems biology
approach, with the goal of elucidating mechanisms mediating the associations between SNPs,
endophenotypes and CVD endpoints from our prior work; (3) to identify genetic and epigenetic
variants associated with novel phenotypes linking psychosocial stress with CVD.

## Key facts

- **NIH application ID:** 9939636
- **Project number:** 5P01HL036587-29
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Svati H. Shah
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $393,185
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939636

## Citation

> US National Institutes of Health, RePORTER application 9939636, Project 3 - Shah (5P01HL036587-29). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9939636. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*