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

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 Asia...

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Published in:European heart journal Vol. 43; no. 18; p. 1702
Main 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
Format: Journal Article
Language:English
Published: England 07.05.2022
Subjects:
Asian People
China - epidemiology
Cohort Studies
Coronary Artery Disease - epidemiology
Coronary Artery Disease - genetics
Genetic Predisposition to Disease - genetics
Genome-Wide Association Study
Humans
Multifactorial Inheritance - genetics
Prospective Studies
Risk Assessment - methods
Risk Factors
China
Polygenic risk score
Clinical risk score
Coronary artery disease
ISSN:1522-9645, 1522-9645
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Summary: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.
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ISSN:1522-9645
1522-9645
DOI:10.1093/eurheartj/ehac093