Associations of polygenic risk scores with risks of stroke and its subtypes in Chinese  

作　　者：Songchun Yang Zhijia Sun Dong Sun Canqing Yu Yu Guo Dianjianyi Sun Yuanjie Pang Pei Pei Ling Yang Iona Y Millwood Robin G Walters Yiping Chen Huaidong Du Yan Lu Sushila Burgess Daniel Avery Robert Clarke Junshi Chen Zhengming Chen Liming Li Jun Lv On behalf of the China Kadoorie Biobank Collaborative Group 

机构地区：[1]Department of Epidemiology&Biostatistics,School of Public Health,Peking University,Beijing,China [2]Department of Dermatology,Xiangya Hospital,Central South University,Changsha,Hunan,China [3]Peking University Center for Public Health and Epidemic Preparedness&Response,Beijing,China [4]Key Laboratory of Epidemiology of Major Diseases(Peking University),Ministry of Education,Beijing,China [5]Fuwai Hospital Chinese Academy of Medical Sciences,Beijing,China [6]Medical Research Council Population Health Research Unit at the University of Oxford,Oxford,UK [7]Clinical Trial Service Unit&Epidemiological Studies Unit(CTSU),Nuffield Department of Population Health,University of Oxford,Oxford,UK [8]NCDs Prevention and Control Department,Suzhou CDC,Suzhou,Jiangsu,China [9]China National Center for Food Safety Risk Assessment,Beijing,China [10]State Key Laboratory of Vascular Homeostasis and Remodeling,Peking University,Beijing,China [11]不详

出　　处：《Stroke & Vascular Neurology》2024年第4期399-406,I0044-I0065,共30页卒中与血管神经病学（英文）

基　　金：supported by the National Natural Science Foundation of China(82192904,82192901,82192900);The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong.The long-term follow-up is supported by grants from the UK Wellcome Trust(212946/Z/18/Z,202922/Z/16/Z,104085/Z/14/Z,088158/Z/09/Z);grants(2016YFC0900500)from the National Key R&D Program of China,National Natural Science Foundation of China(81390540,91846303,81941018);Chinese Ministry of Science and Technology(2011BAI09B01).

摘　　要：Background and purpose Previous studies,mostly focusing on the European population,have reported polygenic risk scores(PRSs)might achieve risk stratification of stroke.We aimed to examine the association strengths of PRSs with risks of stroke and its subtypes in the Chinese population.Methods Participants with genome-wide genotypic data in China Kadoorie Biobank were split into a potential training set(n=22191)and a population-based testing set(n=72150).Four previously developed PRSs were included,and new PRSs for stroke and its subtypes were developed.The PRSs showing the strongest association with risks of stroke or its subtypes in the training set were further evaluated in the testing set.Cox proportional hazards regression models were used to estimate the association strengths of different PRSs with risks of stroke and its subtypes(ischaemic stroke(IS),intracerebral haemorrhage(ICH)and subarachnoid haemorrhage(SAH)).Results In the testing set,during 872919 person-years of follow-up,8514 incident stroke events were documented.The PRSs of any stroke(AS)and IS were both positively associated with risks of AS,IS and ICH(p<0.05).The HR for per SD increment(HR_(SD))of PRSAS was 1.10(95%CI 1.07 to 1.12),1.10(95%CI 1.07 to 1.12)and 1.13(95%CI 1.07 to 1.20)for AS,IS and ICH,respectively.The corresponding HR_(SD) of PRS_(IS) was 1.08(95%CI 1.06 to 1.11),1.08(95%CI 1.06 to 1.11)and 1.09(95%CI 1.03 to 1.15).PRS_(ICH) was positively associated with the risk of ICH(HR_(SD)=1.07,95%CI 1.01 to 1.14).PRSS_(AH) was not associated with risks of stroke and its subtypes.The addition of current PRSs offered little to no improvement in stroke risk prediction and risk stratification.Conclusions In this Chinese population,the association strengths of current PRSs with risks of stroke and its subtypes were moderate,suggesting a limited value for improving risk prediction over traditional risk factors in the context of current genome-wide association study under-representing the East Asian population.

关 键 词：testing PREDICTION INCREMENT 

分 类 号：R743.3[医药卫生—神经病学与精神病学]