# Epigenomic and Metabolomics Determinants of Subclinical and Clinical Vascular and Myocardial Disease

> **NIH NIH P01** · EMORY UNIVERSITY · 2022 · $272,357

## Abstract

PROJECT SUMMARY / ABSTRACT: Project 3
To transform conventional imprecise cardiovascular disease (CVD) risk assessments towards more precise
risk prediction and early-stage detection, Project 3 will conduct an untargeted multi-omic study to investigate
molecular factors associated with subclinical and clinical CVD phenotypes along atherosclerotic CVD (ASCVD)
and heart failure (HF) pathways including HF with preserved (HFpEF) and reduced ejection fraction (HFrEF).
Both genetic and environmental risk factors contribute to the development of CVD. Identified genetic variations
only account for a small proportion of ASCVD and HF risk in the population. Effect of environmental
contributions to CVD, however, remain largely unexplored at the molecular level. Biomolecules, such as
epigenetic and metabolomic markers, can capture complementary molecular effectors in response to
environmental exposures, and alter biological functions at multiple levels. Therefore, studying multiple
molecular layers (e.g., epigenome and metabolome) may help discover novel pathways and mechanisms
through which environmental exposures influence CVD development and provide new targets for prevention
and management of CVD. This is particularly important for populations, such as South Asians, who suffer a
high burden of CVD at young ages and have unique cardiometabolic risk profile (e.g., very high prevalence of
diabetes and dyslipidemia despite relatively low prevalence of obesity), but are underrepresented in current
population studies of epigenomics, metabolomics and genomics. Examining the changes in multi-omic markers
in relation to the natural history of CVD phenotypes within the same individuals provides a controlled and
unbiased evaluation of these relationships. To identify epigenomic and metabolomic factors associated with
subclinical (Aim 1, atherosclerosis and left ventricular systolic/diastolic dysfunction) and clinical CVD (Aim 2,
coronary artery disease, HFpEF, ischemic and non-ischemic HFrEF), we will conduct epigenome-wide and
metabolome-wide association analyses of 3,000 participants informatively selected from the Precision
Cardiovascular Phenotyping and Pathophysiological Pathways in the CARRS cohort (Precision-CARRS),
measured at baseline and the first follow-up visit, and replicate the findings in external cohorts. To determine
the joint impact of genomic, epigenomic and metabolomic profiles on subclinical and clinical CVD and build
prediction models (Aim 3), we will apply advanced multi-omic approaches, machine learning algorithms and
causal inference methods. Lastly, we will assess whether epigenomic and metabolomic profiles are associated
with, and mediate ambient air pollution (from Project 2) in relation to subclinical and clinical CVD (Aim 4).
Through comprehensive multi-omic measurements and integrative analyses, Project 3 will improve the risk
assessment, molecular understanding and precision medicine of CVD in South Asians.

## Key facts

- **NIH application ID:** 10333818
- **Project number:** 1P01HL154996-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Yan Sun
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $272,357
- **Award type:** 1
- **Project period:** 2022-05-15 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10333818

## Citation

> US National Institutes of Health, RePORTER application 10333818, Epigenomic and Metabolomics Determinants of Subclinical and Clinical Vascular and Myocardial Disease (1P01HL154996-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10333818. Licensed CC0.

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