26-A-14188-ACC Performance of Coronary Artery Disease Polygenic Risk Score Testing Using Whole-Genome Sequencing in a Diverse, Real-World Cohort of Cardiovascular Disease Patients
Recommended Citation
Aurora L, Lowry J, Amendola L, Trepanier A, Ferrari H, Cabral W, Strom S, Kesari A, Rajkumar R, Chawla A, Coffey A, Hostin D, Metz H, Hatchell K, Huertas-Vazquez A, Perry D, Longoni M, Taft R, Lanfear DE. 26-A-14188-ACC Performance of Coronary Artery Disease Polygenic Risk Score Testing Using Whole-Genome Sequencing in a Diverse, Real-World Cohort of Cardiovascular Disease Patients. J Am Coll Cardiol 2026; 87(13):A525.
Document Type
Conference Proceeding
Publication Date
4-7-2026
Publication Title
J Am Coll Cardiol
Abstract
Background: It is increasingly recognized that genetic risk for coronary artery disease (CAD) is partly due to polygenic variation. Polygenic risk scores (PRS) based on whole-genome sequencing can quantify this risk, but validation of PRS test performance in real-world clinical populations, particularly across ancestry groups, is still needed. Methods: A prospective clinical cohort of 1,000 patients presenting to Henry Ford Health Cardiology (Detroit, MI) with at least one cardiovascular diagnosis underwent whole-genome testing using the TruGenomeTM CVD Test (Illumina, Inc.). This test includes a research use only ancestry-specific CAD PRS report (Allelica, Inc.) that was developed to identify patients with at least two-fold increased genetic risk for CAD. Here, we examine how CAD PRS test results correspond to prevalent CAD across patient demographic factors and clinical indications. Results: The cohort was half female (n = 499) with a mean age of 67.6 years. Cohort-wide, 40.9% of patients had an indication of cor onary or peripheral arterial disease, 39.1% reported being Black/African American and 57.9% reported being White. Elevated PRS wa found in 44 patients (4.4%), among whom 31 had current diagnosis of CAD (70.5%), a rate 1.78-fold greater than in PRS-negative patients (39.5%). Among patients with known CAD, elevated PRS was threefold more common compared to those without CAD diagnosis (7.58% vs. 2.20%, P < 0.001). Elevated PRS was more common in White vs. Black patients (5.90% vs. 1.02%, P = 0.00025), but the rate of prevalent CAD among patients with an elevated PRS was similar in White and Black patients (76.5% vs. 50.0%, P > 0.05). Conclusion: In this racially diverse cardiology cohort, the Allelica CAD risk PRS correlated to prevalent CAD with roughly a 2-fold risk, and among those without a CAD diagnosis identified 2.2% of patients as having higher lifetime risk for CAD. The PRS was less often elevated among Black participants, perhaps reflecting weaker test performance in this population. Together, these findings illustrate the real-world utility and limitations of CAD PRS testing and highlight the importance of diverse genomic datasets for PRS development.
Volume
87
Issue
13
First Page
A525
