# Project 4 - Kraus

> **NIH NIH P01** · DUKE UNIVERSITY · 2020 · $363,994

## Abstract

ABSTRACT – Project 4: Clinical interventions & gene-by-stress effects on cardiometabolic
endophenotypes
For decades, our combined research groups (Williams, Kraus, Blumenthal, Jiang) have investigated the effects
of psychological stress on cardiovascular disease, and the effects of exercise training, stress reduction and
pharmacologic interventions to modify stress effects on cardiometabolic risk. Drs. Blumenthal's and Jiang's
group has been a leader in intervention studies. Dr. Williams' group has been a leader in attempts to
understand how genetic variation can modify these effects and potentially explain variations in the
effectiveness of lifestyle interventions on cardiovascular outcomes. For example, they have described how
BDNF, EBF1, DRD2, 5HTR2C each have specific gene-by-stress effects modified by other demographic
characteristics that are associated with cardiometabolic phenotypes. However, these effects have been
described primarily using cross-sectional associations in large datasets in studies that were not designed to
investigate intervention effects on these relations. To move the field forward scientifically and to begin to
develop effective clinical interventions to modify the adverse gene-by-stress interactions that we have
identified, we will need to understand whether established lifestyle, behavioral and pharmacologic interventions
can equally affect favorable cardiometabolic effects irrespective of these genetic effects, and conversely,
whether the described gene-by-stress interactions affect the influence of established lifestyle, behavioral and
pharmacologic interventions on cardiometabolic health. A number of important questions remain largely or
totally unexplored in the field. 1) Do clinical interventions designed to target cardiometabolic risk modify or
mollify the adverse gene-by-stress interactions being illuminated in Projects 1 and 2? 2) Do genes, chronic
stress, or gene-by-stress effects predict who will adhere to favorable clinical interventions that favorably
influence cardiometabolic health? 3) Can one demonstrate clinically, using targeted pharmacologic and genetic
testing, that the gene-by-stress interactions that we have identified are really active and are not merely chance
statistical associations? We have brought together a number of unique cohorts from completed lifestyle and
intervention trials to begin to address these important scientific and clinical questions. In this Project 4, we will
be studying the effects of stress-by-gene interactions on intervention effects and the converse in established
cohorts from lifestyle and pharmacologic datasets; the effects of gene-by-stress interactions on adherence to
exercise interventions; and the effects of gene-targeted pharmacologic agents on gene-by-stress effects on
cardiometabolic phenotypes. Molecular data already collected will be provided to Project 3 to identify potential
molecular pathways involved in the observed effects.

## Key facts

- **NIH application ID:** 9939638
- **Project number:** 5P01HL036587-29
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** WILLIAM E KRAUS
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $363,994
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939638

## Citation

> US National Institutes of Health, RePORTER application 9939638, Project 4 - Kraus (5P01HL036587-29). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9939638. Licensed CC0.

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