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

IF 4.4 1区 医学 Q1 CLINICAL NEUROLOGY
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
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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 (HRSD) 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 HRSD of PRSIS 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). PRSICH was positively associated with the risk of ICH (HRSD=1.07, 95% CI 1.01 to 1.14). PRSSAH 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.

中国人的多基因风险评分与中风风险及其亚型的关系。
背景和目的:以往的研究大多集中在欧洲人群,这些研究报告称多基因风险评分(PRSs)可实现脑卒中的风险分层。我们旨在研究多基因风险评分与中国人群中风风险及其亚型的关联强度:方法:将中国嘉道理生物库中拥有全基因组基因型数据的参与者分为潜在训练集(22 191 人)和基于人群的测试集(72 150 人)。其中包括四个以前开发的 PRS,以及针对脑卒中及其亚型开发的新 PRS。在训练集中显示与中风风险或其亚型关系最密切的 PRS 在测试集中得到进一步评估。使用 Cox 比例危险度回归模型估算不同 PRS 与中风及其亚型(缺血性中风(IS)、脑内出血(ICH)和蛛网膜下腔出血(SAH))风险的关联强度:在 872 919 人年的随访过程中,测试组记录了 8514 例中风事件。任何卒中(AS)和 IS 的 PRS 与 AS、IS 和 ICH 的风险均呈正相关(PRSAS 的 pSD 分别为 1.10(95% CI 1.07 至 1.12)、1.10(95% CI 1.07 至 1.12)和 1.13(95% CI 1.07 至 1.20))。PRSIS的相应HRSD分别为1.08(95% CI 1.06至1.11)、1.08(95% CI 1.06至1.11)和1.09(95% CI 1.03至1.15)。PRSICH 与 ICH 风险呈正相关(HRSD=1.07,95% CI 1.01 至 1.14)。PRSSAH 与中风及其亚型的风险无关。增加目前的 PRS 对卒中风险预测和风险分层几乎没有改善:在这一中国人群中,当前 PRS 与脑卒中风险及其亚型的关联强度适中,这表明在当前全基因组关联研究对东亚人群代表性不足的背景下,与传统风险因素相比,当前 PRS 在改善风险预测方面的价值有限。
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来源期刊
Stroke and Vascular Neurology
Stroke and Vascular Neurology Medicine-Cardiology and Cardiovascular Medicine
CiteScore
11.20
自引率
1.70%
发文量
63
审稿时长
15 weeks
期刊介绍: Stroke and Vascular Neurology (SVN) is the official journal of the Chinese Stroke Association. Supported by a team of renowned Editors, and fully Open Access, the journal encourages debate on controversial techniques, issues on health policy and social medicine.
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