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

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.

Genome-wide analyses of early-onset acute myocardial infarction identify 29 novel loci by whole genome sequencing

“…In this study, 596 patients with early-onset AMI from four teaching hospitals in Korea were enrolled and 643 healthy subjects from the Korean Genome Project (KGP) were selected as control (38, 39). Patients with early-onset AMI were hospitalized with a diagnosis and treatment of an ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) caused by atherothrombotic occlusive lesions which were treated with PCI (40). Patients with early-onset AMI included in this study were men and women under 50 and 60 years of age, respectively.…”

“…WGS was performed using the Illumina NovaSeq 6000 platform and clinical information from the KGP was matched (38, 39). Of the 596 patient samples, 265 had already been sequenced in a previous study (40), and the remaining 331 samples were sequenced for this study (Table 1). Genomic DNA was isolated from the plate using a DNeasy Blood & Tissue kit (Qiagen, Germany) according to the manufacturer’s protocol.…”