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Title: A polygenic risk score improves risk stratification of coronary artery disease: a large-scale prospective Chinese cohort study
Authors: Lu, Xiangfeng
Liu, Zhongying
Cui, Qingmei
Liu, Fangchao
Li, Jianxin
Niu, Xiaoge
Shen, Chong
Hu, Dongsheng
Huang, Keyong
Chen, Jichun
Xing, Xiaolong
Zhao, Yingxin
Lu, Fanghong
Liu, Xiaoqing
Cao, Jie
Chen, Shufeng
Ma, Hongxia
Yu, Ling
Wu, Xianping
Wu, Xigui
Li, Ying
Zhang, Huan
Mo, Xingbo
Zhao, Liancheng
Huang, Jianfeng
Wang, Laiyuan
Wen, Wanqing
Shu, Xiao-Ou
Takeuchi, Fumihiko
Koh, Woon-Puay 
Tai, E Shyong 
Cheng, Ching-Yu 
Wong, Tien Yin 
Chang, Xuling 
Chan, Mark Yan-Yee 
Gao, Wei
Zheng, Hong
Chen, Kexin
Chen, Jing
He, Jiang
Tang, Clara Sze-Man
Lam, Karen Siu Ling
Tse, Hung-Fat
Cheung, Chloe Yu Yan
Takahashi, Atsushi
Kubo, Michiaki
Kato, Norihiro
Terao, Chikashi
Kamatani, Yoichiro
Sham, Pak Chung
Heng, Chew-Kiat 
Hu, Zhibin
Chen, Y Eugene
Wu, Tangchun
Shen, Hongbing
Willer, Cristen J
Gu, Dongfeng
Keywords: Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
Coronary artery disease
Polygenic risk score
Clinical risk score
Issue Date: 23-Feb-2022
Citation: Lu, Xiangfeng, Liu, Zhongying, Cui, Qingmei, Liu, Fangchao, Li, Jianxin, Niu, Xiaoge, Shen, Chong, Hu, Dongsheng, Huang, Keyong, Chen, Jichun, Xing, Xiaolong, Zhao, Yingxin, Lu, Fanghong, Liu, Xiaoqing, Cao, Jie, Chen, Shufeng, Ma, Hongxia, Yu, Ling, Wu, Xianping, Wu, Xigui, Li, Ying, Zhang, Huan, Mo, Xingbo, Zhao, Liancheng, Huang, Jianfeng, Wang, Laiyuan, Wen, Wanqing, Shu, Xiao-Ou, Takeuchi, Fumihiko, Koh, Woon-Puay, Tai, E Shyong, Cheng, Ching-Yu, Wong, Tien Yin, Chang, Xuling, Chan, Mark Yan-Yee, Gao, Wei, Zheng, Hong, Chen, Kexin, Chen, Jing, He, Jiang, Tang, Clara Sze-Man, Lam, Karen Siu Ling, Tse, Hung-Fat, Cheung, Chloe Yu Yan, Takahashi, Atsushi, Kubo, Michiaki, Kato, Norihiro, Terao, Chikashi, Kamatani, Yoichiro, Sham, Pak Chung, Heng, Chew-Kiat, Hu, Zhibin, Chen, Y Eugene, Wu, Tangchun, Shen, Hongbing, Willer, Cristen J, Gu, Dongfeng (2022-02-23). A polygenic risk score improves risk stratification of coronary artery disease: a large-scale prospective Chinese cohort study. EUROPEAN HEART JOURNAL 43 (18) : 1702-+. ScholarBank@NUS Repository.
Abstract: AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.
ISSN: 0195668X
DOI: 10.1093/eurheartj/ehac093
Appears in Collections:Staff Publications

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