A polygenic risk score improves risk stratification of coronary artery disease: a large-scale prospective Chinese cohort study-Reference-Cited by-同舟云学术

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

Published:2022-02-23 Issue:18 Volume:43 Page:1702-1711
ISSN:0195-668X
Container-title:European Heart Journal
language:en
Short-container-title:

Author:

Lu Xiangfeng¹,Liu Zhongying¹,Cui Qingmei¹,Liu Fangchao¹,Li Jianxin¹^ORCID,Niu Xiaoge¹,Shen Chong²,Hu Dongsheng³⁴,Huang Keyong¹,Chen Jichun¹,Xing Xiaolong¹,Zhao Yingxin⁵,Lu Fanghong⁵,Liu Xiaoqing⁶,Cao Jie¹,Chen Shufeng¹,Ma Hongxia²^ORCID,Yu Ling⁷,Wu Xianping⁸,Wu Xigui¹,Li Ying¹^ORCID,Zhang Huan⁹,Mo Xingbo⁹,Zhao Liancheng¹,Huang Jianfeng¹,Wang Laiyuan¹,Wen Wanqing¹⁰^ORCID,Shu Xiao-Ou¹⁰^ORCID,Takeuchi Fumihiko¹¹^ORCID,Koh Woon-Puay¹²^ORCID,Tai E Shyong¹³¹⁴,Cheng Ching-Yu¹⁵^ORCID,Wong Tien yin¹⁵¹⁶^ORCID,Chang Xuling¹⁷¹⁸^ORCID,Chan Mark Yan-Yee¹⁹²⁰^ORCID,Gao Wei²¹^ORCID,Zheng Hong²²,Chen Kexin²²,Chen Jing²³,He Jiang²⁴^ORCID,Tang Clara Sze-man²⁵^ORCID,Lam Karen Siu Ling²⁶^ORCID,Tse Hung-fat²⁶^ORCID,Cheung Chloe Yu Yan²⁶,Takahashi Atsushi²⁷²⁸^ORCID,Kubo Michiaki²⁷^ORCID,Kato Norihiro¹¹^ORCID,Terao Chikashi²⁷^ORCID,Kamatani Yoichiro²⁷²⁹^ORCID,Sham Pak Chung³⁰,Heng Chew-Kiat¹⁷^ORCID,Hu Zhibin²,Chen Y Eugene³¹^ORCID,Wu Tangchun³²,Shen Hongbing²^ORCID,Willer Cristen J³¹³³,Gu Dongfeng¹^ORCID

Affiliation:

1. Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100037, China

2. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University , Nanjing 211166, China

3. Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University , Zhengzhou 450001, China

4. Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center , Shenzhen 518071, China

5. Cardio-Cerebrovascular Control and Research Center, Institute of Basic Medicine, Shandong Academy of Medical Sciences , Jinan 250062, China

6. Division of Epidemiology, Guangdong Provincial 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 Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University , Suzhou 215123, China

10. Department of Medicine, Vanderbilt University Medical 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 of Public Health, National University of Singapore and National University Health System , Singapore

14. Department of Medicine, Yong Loo Lin School of Medicine, National University Health System , Singapore

15. Singapore Eye Research Institute, Singapore National Eye Centre , Singapore

16. Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS, Medical School , Singapore

17. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore , Singapore

18. Khoo Teck Puat—National University 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 Third Hospital , Beijing, China

22. Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, Tianjin Key Laboratory of Breast Cancer Prevention and Therapy, 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 of Public Health and Tropical Medicine, and Tulane University Translational Science Institute , New Orleans, LA, USA

25. Department of Surgery, Li Ka Shing Faculty of Medicine, The University 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 Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences , Yokohama, Japan

28. Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center , Osaka, Japan

29. Laboratory of Complex Trait Genomics, Graduate School of Frontier Sciences, The University of Tokyo , Tokyo, Japan

30. Centre for PanorOmic 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

Abstract

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.

Funder

Chinese Academy of Medical Sciences

Innovation Fund for Medical Sciences

National Natural Science Foundation of China

National Key Research and Development Program of China

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine

Link

https://academic.oup.com/eurheartj/article-pdf/43/18/1702/46632132/ehac093.pdf

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