# Project 1 - Williams

> **NIH NIH P01** · DUKE UNIVERSITY · 2020 · $485,241

## Abstract

PROJECT 1 – Gene x Stress interactions' impacts on pathways to cardiometabolic disease
PROJECT SUMMARY
Our program, developed over 25 years of NHLBI support, has identified and continues to identify gene variants
that interact with psychosocial stress to influence, via central nervous system and peripheral mechanisms,
expression of behavioral and physiological endophenotypes in pathways to cardiometabolic disease and
adverse clinical course. During the renewal period Project 1 will extend and substantially refine this work.
Among the major challenges in studying gene by stress interactions are the need for a large number of
individual observations in order to yield adequate statistical power and precision, and the relative absence of
explicit measures of stress in prior studies. Project 1 addresses the first challenge by, in collaboration with the
Biostatistics and Bioinformatics Core, harmonizing a number of large existing datasets, which will in turn be
used to validate previous and newly discovered findings (Aim 1), and to embed those findings in the broader
context of race (African Americans and Caucasians) (Aim 2) and potential mediating mechanisms that are
thought to link variants to cardiometabolic disease. Project 1 overcomes the absence of explicit measures of
stress by constructing a synthetic index of stress using bioinformatics techniques, which have proven
successful in our preliminary work. We also will continue our discovery approach using high-throughput
computational bioinformatics approaches, and gene x stress GWAS will be used in large publically accessible
databases (e.g., MESA, FHS, CARDIA. Jackson Heart Study) to identify new gene variants associated with
cardiometabolic endophenotypes (Aim 3). These newly discovered variants will be validated in new data
derived from the harmonization. Project 1 also will pass previously and newly identified gene variants
associated, both directly and via interaction with stress, with cardiometabolic endophenotypes to Project 2 (to
test for effects on endophenotypes in pathways to type 2 diabetes), Project 3 (to test for effects on epigenetic,
transcriptomic and metabolomics mechanism that mediate effects on endophenotypes and disease endpoints),
and Project 4 (to test for effects on response of endophenotypes to behavioral and drug interventions).
Successful completion of these aims will increase our understanding of gene x stress interactions that link
stress to the development and course of cardiometabolic disease, knowledge that will be critical for the
ultimate development of effective preventive and treatment interventions.

## Key facts

- **NIH application ID:** 9939629
- **Project number:** 5P01HL036587-29
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Redford B WILLIAMS
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $485,241
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939629

## Citation

> US National Institutes of Health, RePORTER application 9939629, Project 1 - Williams (5P01HL036587-29). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9939629. Licensed CC0.

---

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