R01HL158884

Genome-Wide Association Study of Coronary Artery Disease in Individuals of African Ancestry - 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 studies 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, multivariate 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.

Vanderbilt University Medical Center

TO FOSTER HEART AND VASCULAR RESEARCH IN THE BASIC, TRANSLATIONAL, CLINICAL AND POPULATION SCIENCES, AND TO FOSTER TRAINING TO BUILD TALENTED YOUNG INVESTIGATORS IN THESE AREAS, FUNDED THROUGH COMPETITIVE RESEARCH TRAINING GRANTS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Nashville, Tennessee 37203 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the End Date has been extended from 07/31/25 to 07/31/26 and the total obligations have increased 262% from $832,106 to $3,009,772.