Faculty, Staff and Student Publications

Language

English

Publication Date

2-18-2025

Journal

Journal of the American Heart Association

DOI

10.1161/JAHA.124.036499

PMID

39950338

PMCID

PMC12074758

PubMedCentral® Posted Date

2-14-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Genome-wide association studies have identified several hundred susceptibility single nucleotide variants for coronary artery disease (CAD). Despite single nucleotide variant-based genome-wide association studies improving our understanding of the genetics of CAD, the contribution of structural variants (SVs) to the risk of CAD remains largely unclear.

Method and results: We leveraged SVs detected from high-coverage whole genome sequencing data in a diverse group of participants from the National Heart Lung and Blood Institute's Trans-Omics for Precision Medicine program. Single variant tests were performed on 58 706 SVs in a study sample of 11 556 CAD cases and 42 907 controls. Additionally, aggregate tests using sliding windows were performed to examine rare SVs. One genome-wide significant association was identified for a common biallelic intergenic duplication on chromosome 6q21 (P=1.54E-09, odds ratio=1.34). The sliding window-based aggregate tests found 1 region on chromosome 17q25.3, overlapping USP36, to be significantly associated with coronary artery disease (P=1.03E-10). USP36 is highly expressed in arterial and adipose tissues while broadly affecting several cardiometabolic traits.

Conclusions: Our results suggest that SVs, both common and rare, may influence the risk of coronary artery disease.

Keywords

Humans, Coronary Artery Disease, Genome-Wide Association Study, Male, Female, Genetic Predisposition to Disease, Middle Aged, Aged, Polymorphism, Single Nucleotide, Case-Control Studies, Genomic Structural Variation, Whole Genome Sequencing, Chromosomes, Human, Pair 6, Phenotype, Risk Factors, association testing, coronary artery disease, genetics, structural variants, whole‐genome sequencing

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.