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

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $763,120

## 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 and East-Asian ancestries and identified 207 independent loci so
far. Few of the identified loci have been replicated in populations of African ancestries. Large-scale genetic study
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 genomic
analyses 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:** 10459545
- **Project number:** 5R01HL158884-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Yingchang Lu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $763,120
- **Award type:** 5
- **Project period:** 2021-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459545

## Citation

> US National Institutes of Health, RePORTER application 10459545, Genome-wide association study of coronary artery disease in individuals of African ancestry (5R01HL158884-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10459545. Licensed CC0.

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