Bioscience and Biomedical Engineering Thrust, Systems Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong, China.
School of Public Health, Fudan University, Shanghai, China.
Brain Behav Immun. 2024 Aug;120:352-359. doi: 10.1016/j.bbi.2024.06.016. Epub 2024 Jun 17.
Experimental and cross-sectional evidence has suggested a potential role of infection in the ethology of Parkinson's disease (PD). We aim to examine the longitudinal association of infections with the incidence of PD and to explore whether the increased risk is limited to specific infection type rather than infection burden.
Based on the UK Biobank, hospital-treated infectious diseases and incident PD were ascertained through record linkage to national hospital inpatient registers. Infection burden was defined as the sum of the number of infection episodes over time and the number of co-occurring infections. The polygenic risk score (PRS) for PD was calculated. The genome-wide association studies (GWAS) used in two-sample Mendelian Randomization (MR) were obtained from observational cohort participants of mostly European ancestry.
Hospital-treated infectious diseases were associated with an increased risk of PD (adjusted HR [aHR] 1.35 [95 % CI 1.20-1.52]). This relationship persisted when analyzing new PD cases occurring more than 10 years post-infection (aHR 1.22 [95 % CI 1.04-1.43]). The greatest PD risk was observed in neurological/eye infection (aHR 1.72 [95 % CI 1.32-2.34]), with lower respiratory tract infection (aHR 1.43 [95 % CI 1.02-1.99]) ranked the second. A dose-response association was observed between infection burden and PD risk within each PD-PRS tertile (p-trend < 0.001). Multivariable MR showed that bacterial and viral infections increase the PD risk.
Both observational and genetic analysis suggested a causal association between infections and the risk of developing PD. A dose-response relationship between infection burden and incident PD was revealed.
实验和横断面证据表明，感染可能在帕金森病（PD）的发病机制中起作用。我们旨在研究感染与 PD 发病的纵向关联，并探讨增加的风险是否仅限于特定的感染类型，而不是感染负担。
基于英国生物银行（UK Biobank），通过与国家住院患者登记处的记录链接，确定医院治疗的传染病和 PD 的发病情况。感染负担定义为随着时间的推移感染次数的总和以及同时发生的感染次数。PD 的多基因风险评分（PRS）是计算的。两样本孟德尔随机化（MR）中使用的全基因组关联研究（GWAS）是从主要为欧洲血统的观察队列参与者中获得的。
医院治疗的传染病与 PD 的发病风险增加有关（调整后的 HR [aHR] 1.35 [95%CI 1.20-1.52]）。当分析感染后 10 年以上发生的新 PD 病例时，这种关系仍然存在（aHR 1.22 [95%CI 1.04-1.43]）。在神经系统/眼部感染中观察到最大的 PD 风险（aHR 1.72 [95%CI 1.32-2.34]），下呼吸道感染的风险次之（aHR 1.43 [95%CI 1.02-1.99]）。在每个 PD-PRS 三分位内，感染负担与 PD 风险之间观察到剂量反应关系（p 趋势 <0.001）。多变量 MR 表明细菌和病毒感染会增加 PD 的风险。
观察性和遗传分析均表明感染与 PD 发病风险之间存在因果关系。感染负担与新发 PD 之间存在剂量反应关系。
