Integrating polygenic and clinical risks to improve stroke risk stratification in prospective Chinese cohorts
作者机构：Department of EpidemiologyFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100037China Key Laboratory of Cardiovascular EpidemiologyChinese Academy of Medical SciencesBeijing100037China Department of NephrologyHenan 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 BiostatisticsCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing211166China Department of Epidemiology and Health StatisticsCollege of Public HealthZhengzhou UniversityZhengzhou450001China Department of Prevention MedicineShenzhen University School of MedicineShenzhen518060China Division of EpidemiologyGuangdong Provincial People’s Hospital and Cardiovascular InstituteGuangzhou510080China Department of CardiologyFujian Provincial People’s HospitalFuzhou350014China Cardio-Cerebrovascular Control and Research CenterInstitute of Basic MedicineShandong Academy of Medical SciencesJinan250062China Sichuan Center for Disease Control and PreventionChengdu610041China Research Units of Cohort Study on Cardiovascular Diseases and CancersChinese Academy of Medical SciencesBeijing100730China School of MedicineSouthern University of Science and TechnologyShenzhen518055China
出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)
年 卷 期：2023年第66卷第7期
页 面：1626-1635页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 100204[医学-神经病学] 10[医学]
基 金：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-GSPGG-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 91857118) Taikang Yicai Public Health and Epidemic Control Fund(TKYC-GW-2020) the National Clinical Research Center for Cardiovascular Diseases,Fuwai Hospital,Chinese Academy of Medical Sciences(NCRC2020006)。
主 题：stroke polygenic risk score clinical risk score utility stratification
摘 要：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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