# Cardiovascular Disease Risk Factors, Cardiovascular Disease Risk Prediction, and Genetics in the Million Veteran Program

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2024 · —

## Abstract

Cardiovascular disease (CVD) risk estimation has historically focused on outpatient data from
whites according to age, sex, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), diabetes,
smoking, and blood pressure (BP) information. Risk factors (RFs) and overall CVD risk are
associated with genetic variations in genome-wide association studies (GWAS), and
phenotypes have largely been based on single RF measurements using a Framingham
approach. Previous research has focused on European Americans (EA), and generally has not
included Veterans. Little information on CVD risk factor genes is available for African
Americans (AA) or Hispanic Americans (HA), two population groups that are extremely
important in the VA. The Million Veteran Program (MVP) cohort provides a unique opportunity
to study genes and CVD risk among these subgroups, using MVP questionnaire data, electronic
health record (EHR) information, and genetic data. We propose to address scientific gaps by
focusing on multiple ethnicities, rare variants, and antecedent RF levels using the MVP cohort.
In previous funding we created a virtual baseline exam for all MVP participants and we propose
to further curate that information, extend research into new heart disease RFs and conditions,
and use a longitudinal prospective study design. In addition to traditional CVD RFs such as
lipids, smoking, diabetes, and BP that are already under investigation by our MVP research
group, we propose to use GWAS to assess effects of genes on blood cell indices, inflammatory
conditions, valvular heart disease, obstructive sleep apnea, and atrial fibrillation. Our research
will assess gene-environment (diet quality, pharmacological treatment) effects, and will included
assessment of current and antecedent RF levels. Methods will include diet quality adjustments
using the Willett Food Frequency Questionnaire performed at the MVP baseline visit. Other
methods will include pharmacologic treatment of CVD RFs to derive imputed untreated RF
levels, and antecedent quantitative CVD RFs measured at VA outpatient visits up to 14 years
before the MVP baseline visit when such data are available. We will perform common variant
association studies (CVAS) and rare variant association studies (RVAS), testing for the
association of genetic variants to quantitative CVD risk for incidence and period prevalence of a)
coronary heart disease (CHD) [myocardial infarction (MI), coronary bypass grafting (CABG),
percutaneous coronary intervention (PCI)] and b) atherothrombotic stroke, with comparison of
effects by race and ethnicity, and c) recurrent events following an initial MI or stroke. Summary
analyses will examine the multigenic association of CHD and stroke using the genetic risk score
(GRS) of validated CVD-associated SNPs within and across ethnicity. This project will provide
a platform for CVD incidence analyses for MVP participants across the VA in the future. The
proposed study findings will allow for the comparison of the i...

## Key facts

- **NIH application ID:** 10830906
- **Project number:** 5I01BX004821-05
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** PETER WYMAN WILSON
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-10-01 → 2026-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10830906

## Citation

> US National Institutes of Health, RePORTER application 10830906, Cardiovascular Disease Risk Factors, Cardiovascular Disease Risk Prediction, and Genetics in the Million Veteran Program (5I01BX004821-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10830906. Licensed CC0.

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