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Integrating polygenic and clinical risks to improve stroke risk stratification in prospective Chinese cohorts

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Abstract

The utility of the polygenic risk score (PRS) to identify individuals at higher risk of stroke beyond clinical risk remains unclear, and we clarified this using Chinese population-based prospective cohorts. Cox proportional hazards models were used to estimate the 10-year risk, and Fine and Gray’s models were used for hazard ratios (HRs), their 95% confidence intervals (CIs), and the lifetime risk according to PRS and clinical risk categories. A total of 41,006 individuals aged 30–75 years with a mean follow-up of 9.0 years were included. Comparing the top versus bottom 5% of the PRS, the HR was 3.01 (95%CI 2.03–4.45) in the total population, and similar findings were observed within clinical risk strata. Marked gradients in the 10-year and lifetime risk across PRS categories were also found within clinical risk categories. Notably, among individuals with intermediate clinical risk, the 10-year risk for those in the top 5% of the PRS (7.3%, 95%CI 7.1%–7.5%) reached the threshold of high clinical risk (⩾7.0%) for initiating preventive treatment, and this effect of the PRS on refining risk stratification was evident for ischemic stroke. Even among those in the top 10% and 20% of the PRS, the 10-year risk would also exceed this level when aged ⩾50 and ⩾60 years, respectively. Overall, the combination of the PRS with the clinical risk score improved the risk stratification within clinical risk strata and distinguished actual high-risk individuals with intermediate clinical risk.

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Acknowledgements

This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2021-I2M-1-010, 2019-I2M-2-003, and 2017-I2M-1-004), the National High Level Hospital Clinical Research Funding (2022-GSP-GG-1, 2022-GSP-GG-2), Research Unit of Prospective Cohort of Cardiovascular Diseases and Cancers, CAMS (2019RU038), the National Key Research and Development Program of China (2018YFE0115300 and 2017YFC0211700), the National Natural Science Foundation of China (82030102, 12126602, and 91857118), Taikang Yicai Public Health and Epidemic Control Fund (TKYC-GW-2020) and the National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences (NCRC2020006). We acknowledged the staff and participants from the China-PAR project for their participation and contribution.

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  1. Contributed equally to this work

Authors and Affiliations

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

    Qingmei Cui, Fangchao Liu, Jianxin Li, Xiaoge Niu, Zhongying Liu, Keyong Huang, Shufeng Chen, Jie Cao, Liancheng Zhao, Jianfeng Huang, Ying Li, Dongfeng Gu & Xiangfeng Lu

  2. Key Laboratory of Cardiovascular Epidemiology, Chinese Academy of Medical Sciences, Beijing, 100037, China

    Qingmei Cui, Fangchao Liu, Dongfeng Gu & Xiangfeng Lu

  3. Department of Nephrology, Henan Provincial Key Laboratory of Kidney Disease and Immunology, Henan Provincial Clinical Research Center for Kidney Disease, Henan Provincial People’s Hospital and People’s Hospital of Zhengzhou University, Zhengzhou, 450053, China

    Xiaoge Niu

  4. Department of Epidemiology and Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    Chong Shen, Zhibin Hu & Hongbing Shen

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

    Dongsheng Hu

  6. Department of Prevention Medicine, Shenzhen University School of Medicine, Shenzhen, 518060, China

    Dongsheng Hu

  7. Division of Epidemiology, Guangdong Provincial People’s Hospital and Cardiovascular Institute, Guangzhou, 510080, China

    Xiaoqing Liu

  8. Department of Cardiology, Fujian Provincial People’s Hospital, Fuzhou, 350014, China

    Ling Yu

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

    Fanghong Lu

  10. Sichuan Center for Disease Control and Prevention, Chengdu, 610041, China

    Xianping Wu

  11. Research Units of Cohort Study on Cardiovascular Diseases and Cancers, Chinese Academy of Medical Sciences, Beijing, 100730, China

    Hongbing Shen

  12. School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China

    Dongfeng Gu

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  1. Qingmei Cui
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  2. Fangchao Liu
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  3. Jianxin Li
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  4. Xiaoge Niu
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  8. Keyong Huang
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  19. Hongbing Shen
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  20. Dongfeng Gu
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  21. Xiangfeng Lu
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Corresponding authors

Correspondence to Dongfeng Gu or Xiangfeng Lu.

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The authors declare that they have no conflict of interest. This study was approved by the Institutional Review Board at Fuwai Hospital in Beijing, China.

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Cui, Q., Liu, F., Li, J. et al. Integrating polygenic and clinical risks to improve stroke risk stratification in prospective Chinese cohorts. Sci. China Life Sci. 66, 1626–1635 (2023). https://doi.org/10.1007/s11427-022-2280-3

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