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A polygenic risk score improves risk stratification of coronary artery disease: a large-scale prospective Chinese cohort study.

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机构: [1]Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center forCardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China [2]Department of Epidemiology and Biostatistics, School ofPublic Health, Nanjing Medical University, Nanjing 211166, China [3]Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou450001, China [4]Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen 518071, China [5]CardioCerebrovascular Control and Research Center, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan 250062, China [6]Division of Epidemiology, GuangdongProvincial People’s Hospital and Cardiovascular Institute, Guangzhou 510080, China [7]Department of Cardiology, Fujian Provincial People’s Hospital, Fuzhou 350014, China [8]Sichuan Center for Disease Control and Prevention, Chengdu 610041, China [9]Center for Genetic Epidemiology and Genomics, School of Public Health and Jiangsu Key Laboratoryof Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China [10]Department of Medicine, Vanderbilt UniversityMedical Center, Nashville, TN, USA [11]Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan [12]Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore [13]Saw Swee Hock School ofPublic Health, National University of Singapore and National University Health System, Singapore [14]Department of Medicine, Yong Loo Lin School of Medicine, National UniversityHealth System, Singapore [15]Singapore Eye Research Institute, Singapore National Eye Centre, Singapore [16]Ophthalmology and Visual Sciences Academic Clinical Program, DukeNUS, Medical School, Singapore [17]Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore [18]Khoo Teck Puat—NationalUniversity Children’s Medical Institute, National University Health System, Singapore [19]Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore,Singapore [20]National University Heart Centre, National University Health System, Singapore [21]Department of Cardiology, Institute of Vascular Medicine, Peking University ThirdHospital, Beijing, China [22]Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Breast Cancer Prevention andTherapy, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China [23]Department of Medicine,Tulane University School of Medicine, and Tulane University Translational Science Institute, New Orleans, LA, USA [24]Department of Epidemiology, Tulane University School ofPublic Health and Tropical Medicine, and Tulane University Translational Science Institute, New Orleans, LA, USA [25]Department of Surgery, Li Ka Shing Faculty of Medicine, TheUniversity of Hong Kong, Hong Kong, China [26]Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China [27]Laboratory for Statisticaland Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan [28]Department of Genomic Medicine, Research Institute, National Cerebral andCardiovascular Center, Osaka, Japan [29]Laboratory of Complex Trait Genomics, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan [30]Centre forPanorOmic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China [31]Department of Internal Medicine, Division of Cardiovascular Medicine,University of Michigan, Ann Arbor, MI, USA [32]MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science &Technology, Wuhan 430030, China [33]Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
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关键词: Coronary artery disease • Polygenic risk score • Clinical risk score

摘要:
To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations.Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS.The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.The incorporation of polygenic risk into clinical care setting may provide a valuable risk stratification guidance to identify high-risk individuals for targeted intervention in primary prevention of CAD.© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

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大类 | 1 区 医学
小类 | 1 区 心脏和心血管系统
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大类 | 1 区 医学
小类 | 1 区 心脏和心血管系统
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Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
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Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

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第一作者机构: [1]Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center forCardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
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