Youngjune Bhak1,2, Yeonsu Jeon1,2, Sungwon Jeon1,2, Changhan Yoon1,2, Min Kim1,2, Asta Blazyte1,2, Yeonkyung Kim1, Younghui Kang1, Changjae Kim3, Sang Yeub Lee4, Jang-Whan Bae4, Weon Kim5, Yeo Jin Kim1, Jungae Shim1, Nayeong Kim1, Sung Chun6,7, Byoung-Chul Kim3, Byung Chul Kim3, Semin Lee1,2, Jong Bhak1,2,3,8, Eun-Seok Shin8,9. 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.
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.
Authors: Donald E Cutlip; Stephan Windecker; Roxana Mehran; Ashley Boam; David J Cohen; Gerrit-Anne van Es; P Gabriel Steg; Marie-angèle Morel; Laura Mauri; Pascal Vranckx; Eugene McFadden; Alexandra Lansky; Martial Hamon; Mitchell W Krucoff; Patrick W Serruys Journal: Circulation Date: 2007-05-01 Impact factor: 29.690
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Authors: Amit V Khera; Connor A Emdin; Isabel Drake; Pradeep Natarajan; Alexander G Bick; Nancy R Cook; Daniel I Chasman; Usman Baber; Roxana Mehran; Daniel J Rader; Valentin Fuster; Eric Boerwinkle; Olle Melander; Marju Orho-Melander; Paul M Ridker; Sekar Kathiresan Journal: N Engl J Med Date: 2016-11-13 Impact factor: 91.245