# Genome-wide association study of coronary artery diseases in individuals of African ancestry

> **NIH NIH R56** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $934,617

## Abstract

PROJECT SUMMARY/ABSTRACT
Coronary artery disease (CAD) is a leading cause of death among adults in the United States. Its prevalence is
highest in individuals of African ancestry. It has been estimated that genetic factors account for 26% to 69% of
interindividual variation in CAD risk. Large-scale genome-wide association studies (GWAS) of CAD have mainly
been conducted in populations of European ancestry and identified 161 independent loci so far. Few of the loci
identified in European-ancestry populations have been replicated in populations of African ancestry. Large-scale
GWAS of CAD in African-ancestry populations are lacking. This proposal will efficiently leverage the existing
resources of the Population Architecture using Genomics and Epidemiology Consortium, Million Veteran
Program and other established cohorts to create the largest-ever sample size for a genetic study of African-
ancestry populations comprehensively phenotyped for CAD and related cardiometabolic traits. We propose to
address the following Specific Aims. Aim 1 will interrogate the genome using admixture mapping, univariate
GWAS, multi-variate GWAS and trans-ethnic GWAS approaches to identify loci associated with CAD in African-
ancestry populations. Aim 2 will use phenome-wide association studies, variant-trait hierarchical clustering and
integrative genomics methods to characterize CAD loci and gain insights into phenotypic, physiologic, and
mechanistic impacts that underlie the pathophysiology of CAD. Aim 3 will explore the public health impact and
clinical relevance of CAD risk variants by constructing polygenic CAD risk scores and identifying pathogenic
variants in Mendelian syndromes of CAD genes that are relevant to African-ancestry populations. The
construction of population-specific polygenic risk scores and identification of rare and low-frequency pathogenic
variants of large effect in Mendelian syndromes of CAD genes will facilitate quantification of CAD risk in
individuals of African ancestry and potentially narrow the translational gap towards clinical use of genetic
information across diverse populations. The comprehensive cross-trait associations of identified CAD risk loci
will facilitate the discovery of subtypes of CAD. Both improved genetic CAD risk classifications and refined CAD
sub-phenotyping would help with the implementation of precision medicine in CAD. The new biological insights
elucidated from novel loci identified in African-ancestry populations may also be generalized to other populations
for the diagnosis, prevention, and treatment of CAD.

## Key facts

- **NIH application ID:** 10241644
- **Project number:** 1R56HL150186-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Yingchang Lu
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $934,617
- **Award type:** 1
- **Project period:** 2020-09-17 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241644

## Citation

> US National Institutes of Health, RePORTER application 10241644, Genome-wide association study of coronary artery diseases in individuals of African ancestry (1R56HL150186-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10241644. Licensed CC0.

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