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

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; China Kadoorie Biobank Collaborative Group

doi:10.1136/svn-2023-002428

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

Stroke Vasc Neurol. 2023 Aug 28:svn-2023-002428. doi: 10.1136/svn-2023-002428. Online ahead of print.

Authors

Songchun Yang^{1

2}, Zhijia Sun¹, Dong Sun¹, Canqing Yu^{1

3

4}, Yu Guo⁵, Dianjianyi Sun^{1

3

4}, Yuanjie Pang^{1

4}, Pei Pei³, Ling Yang^{6

7}, Iona Y Millwood^{6

7}, Robin G Walters^{6

7}, Yiping Chen^{6

7}, Huaidong Du^{6

7}, Yan Lu⁸, Sushila Burgess⁷, Daniel Avery⁷, Robert Clarke⁷, Junshi Chen⁹, Zhengming Chen⁷, Liming Li^{1

3

4}, Jun Lv^{10

3

4

11}; China Kadoorie Biobank Collaborative Group

Collaborators

China Kadoorie Biobank Collaborative Group:
Junshi Chen, Zhengming Chen, Robert Clarke, Rory Collins, Yu Guo, Liming Li, Jun Lv, Richard Peto, Robin Walters, Daniel Avery, Derrick Bennett, Ruth Boxall, Sue Burgess, Ka Hung Chan, Yumei Chang, Yiping Chen, Zhengming Chen, Johnathan Clarke, Robert Clarke, Huaidong Du, Ahmed Edris Mohamed, Zammy Fairhurst-Hunter, Hannah Fry, Simon Gilbert, Alex Hacker, Mike Hill, Michael Holmes, Pek Kei Im, Andri Iona, Maria Kakkoura, Christiana Kartsonaki, Rene Kerosi, Kuang Lin, Mohsen Mazidi, Iona Millwood, Sam Morris, Qunhua Nie, Alfred Pozarickij, Paul Ryder, Saredo Said, Sam Sansome, Dan Schmidt, Paul Sherliker, Rajani Sohoni, Becky Stevens, Iain Turnbull, Robin Walters, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang, Pang Yao, Yu Guo, Xiao Han, Can Hou, Jun Lv, Pei Pei, Chao Liu, Canqing Yu, Qingmei Xia, Zengchang Pang, Ruqin Gao, Shanpeng Li, Haiping Duan, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang, Yaoming Zhai, Feng Ning, Xiaohui Sun, Feifei Li, Silu Lv, Junzheng Wang, Wei Hou, Wei Sun, Shichun Yan, Xiaoming Cui, Chi Wang, Zhenyuan Wu, Yanjie Li, Quan Kang, Huiming Luo, Tingting Ou, Xiangyang Zheng, Zhendong Guo, Shukuan Wu, Yilei Li, Huimei Li, Ming Wu, Yonglin Zhou, Jinyi Zhou, Ran Tao, Jie Yang, Jian Su, Fang Liu, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, Jianrong Jin, Jingchao Liu, Mei Lin, Zhenzhen Lu, Lifang Zhou, Changping Xie, Jian Lan, Tingping Zhu, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Yulu Qin, Sisi Wang, Xianping Wu, Ningmei Zhang, Xiaofang Chen, Xiaoyu Chang, Mingqiang Yuan, Xia Wu, Xiaofang Chen, Wei Jiang, Jiaqiu Liu, Qiang Sun, Faqing Chen, Xiaolan Ren, Caixia Dong, Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi Zhang, Kai Kang, Shixian Feng, Huizi Tian, Lei Fan, Xiao Li, Huarong Sun, Pan He, Xukui Zhang, Min Yu, Ruying Hu, Hao Wang, Xiaoyi Zhang, Yuan Cao, Kaixu Xie, Lingli Chen, Dun Shen, Xiaojun Li, Donghui Jin, Huilin Liu Li Yin, Zhongxi Fu, Xin Xu, Hao Zhang, Jianwei Chen, Yuan Peng, Libo Zhang, Chan Qu

Affiliations

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 Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing, China lvjun@bjmu.edu.cn.
¹¹ State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.

PMID: 37640499
DOI: 10.1136/svn-2023-002428

Abstract

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=22 191) and a population-based testing set (n=72 150). 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 872 919 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 PRS_AS 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). PRS_SAH 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.

Keywords: Genetics; Prospective Studies; Stroke.

Abstract

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