Polygenic Risk Scores in a Prospective Parkinson's Disease Cohort.

Polygenic Risk Scores in a Prospective Parkinson's Disease Cohort.
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DOI:
10.1002/mds.28761
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发表时间:
2021-12
期刊:
Movement disorders : official journal of the Movement Disorder Society
影响因子:
--
通讯作者:
Tan LC
Tan LC
中科院分区:
其他
文献类型:
--
作者:
Sia MW;Foo JN;Saffari SE;Wong AS;Khor CC;Yuan JM;Tan EK;Koh WP;Tan LC

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亚洲人群缺乏帕金森氏病(PD)特定种族的遗传风险评估框架。在一个基于人群的亚洲前瞻性队列中,我们调查了多基因风险评分(Prs)与帕金森病发病率的关系。新加坡华人健康研究队列中的25,646名参与者前瞻性地收集了遗传、饮食和生活方式的信息。PRS是用亚洲特有的和顶级的GWA变异体构建的。多变量COX比例风险模型、Kaplan-Meier生存分析和一致性统计分析评价了PR与PD发生率之间的关系。经过20多年的跟踪调查,发现了333起事件。在调整饮食和生活方式的危险因素后,上三分位数(HR=1.81,95%CI=1.37~2.39)和中三分位数(HR=1.35,95%CI=1.00~1.83)的患者发生帕金森病的风险较高,Kaplan-Meier生存分析中发生帕金森病的时间较短(p<0.001)。在调整了饮食和生活方式因素后,我们在一个前瞻性的中国队列中发现了与帕金森病发病率显著相关的帕金森病。
Ethnic-specific genetic risk assessment framework for Parkinson’s Disease (PD) is lacking for Asian population. We investigated the association of a polygenic risk score (PRS) with PD incidence in a population-based Asian prospective cohort. Genetic, dietary and lifestyle information were prospectively collected from 25,646 participants within the Singapore Chinese Health Study cohort. PRS was constructed with Asian-specific and top GWAS variants. Association between PRS and PD incidence was evaluated with multivariable Cox proportional hazard model, Kaplan-Meier survival analysis and concordance statistics. Three hundred and thirty-three incident cases were identified after a follow-up period of over 20 years. Participants with PRS in the top tertile (HR=1.81, 95%CI=1.37–2.39) and middle tertile (HR=1.35, 95%CI=1.00–1.83) are at higher risk of developing PD after adjusting for dietary and lifestyle risk factors, with a shorter time to PD event in Kaplan-Meier survival analysis (p<0.001). We identified a PRS that was significantly associated with PD incidence in a prospective Chinese cohort after adjusting for dietary and lifestyle factors.
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