Polygenic risk score validation using Korean genomes of 265 early-onset acute myocardial infarction patients and 636 healthy controls.

Affiliation

Bhak Y(1)(2), Jeon Y(1)(2), Jeon S(1)(2), Yoon C(1)(2), Kim M(1)(2), Blazyte A(1)(2), Kim Y(1), Kang Y(1), Kim C(3), Lee SY(4), Bae JW(4), Kim W(5), Kim YJ(1), Shim J(1), Kim N(1), Chun S(6)(7), Kim BC(3), Kim BC(3), Lee S(1)(2), Bhak J(1)(2)(3)(8), Shin ES(8)(9).
Author information:
(1)Korean Genomics Center
(KOGIC), Ulsan National Institute of Science and Technology
(UNIST), Ulsan, Republic of Korea.
(2)Department of Biomedical Engineering, School of Life Sciences, Ulsan National Institute of Science and Technology
(UNIST), Ulsan, Republic of Korea.
(3)Clinomics Inc, Ulsan, Republic of Korea.
(4)Division of Cardiology, Department of Internal Medicine, Chungbuk National University, College of Medicine, Cheongju, Republic of Korea.
(5)Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea.
(6)Division of Pulmonary Medicine, Boston Children's Hospital, Boston, Massachusetts, United States of America.
(7)Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America.
(8)Personal Genomics Institute, Genome Research Foundation, Ulsan, Republic of Korea.
(9)Division of Cardiology, Department of Internal Medicine, Ulsan Medical Center, Ulsan, Republic of Korea.

Abstract

BACKGROUND: The polygenic risk score (PRS) developed for coronary artery disease (CAD) is known to be effective for classifying patients with CAD and predicting subsequent events. However, the PRS was developed mainly based on the analysis of Caucasian genomes and has not been validated for East Asians. We aimed to evaluate the PRS in the genomes of Korean early-onset AMI patients (n = 265, age ≤50 years) following PCI and controls (n = 636) to examine whether the PRS improves risk prediction beyond conventional risk factors. RESULTS: The odds ratio of the PRS was 1.83 (95% confidence interval [CI]: 1.69-1.99) for early-onset AMI patients compared with the controls. For the classification of patients, the area under the curve (AUC) for the combined model with the six conventional risk factors (diabetes mellitus, family history of CAD, hypertension, body mass index, hypercholesterolemia, and current smoking) and PRS was 0.92 (95% CI: 0.90-0.94) while that for the six conventional risk factors was 0.91 (95% CI: 0.85-0.93). Although the AUC for PRS alone was 0.65 (95% CI: 0.61-0.69), adding the PRS to the six conventional risk factors significantly improved the accuracy of the prediction model (P = 0.015). Patients with the upper 50% of PRS showed a higher frequency of repeat revascularization (hazard ratio = 2.19, 95% CI: 1.47-3.26) than the others. CONCLUSIONS: The PRS using 265 early-onset AMI genomes showed improvement in the identification of patients in the Korean population and showed potential for genomic screening in early life to complement conventional risk prediction.