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

Science China(Life Sciences) 2023年第7期66卷 1626-1635页

作者： Qingmei Cui Fangchao Liu Jianxin Li Xiaoge Niu Zhongying Liu Chong Shen Dongsheng Hu Keyong Huang Shufeng Chen Jie Cao Xiaoqing Liu Ling Yu Fanghong Lu Xianping Wu Liancheng Zhao Jianfeng Huang Ying Li Zhibin Hu Hongbing Shen Dongfeng Gu Xiangfeng Lu Department of Epidemiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100037China Key Laboratory of Cardiovascular Epidemiology Chinese Academy of Medical SciencesBeijing100037China Department of Nephrology Henan Provincial Key Laboratory of Kidney Disease and ImmunologyHenan Provincial Clinical Research Center for Kidney DiseaseHenan Provincial People’s Hospital and People’s Hospital of Zhengzhou UniversityZhengzhou450053China Department of Epidemiology and Biostatistics Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing211166China Department of Epidemiology and Health Statistics College of Public HealthZhengzhou UniversityZhengzhou450001China Department of Prevention Medicine Shenzhen University School of MedicineShenzhen518060China Division of Epidemiology Guangdong Provincial People’s Hospital and Cardiovascular InstituteGuangzhou510080China Department of Cardiology Fujian Provincial People’s HospitalFuzhou350014China Cardio-Cerebrovascular Control and Research Center Institute of Basic MedicineShandong Academy of Medical SciencesJinan250062China Sichuan Center for Disease Control and Prevention Chengdu610041China Research Units of Cohort Study on Cardiovascular Diseases and Cancers Chinese Academy of Medical SciencesBeijing100730China School of Medicine Southern University of Science and TechnologyShenzhen518055China

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.

关键词： stroke polygenic risk score clinical risk score utility stratification

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