某些病毒感染与神经退行性疾病的发展有关。本研究旨在探讨巨细胞病毒 (CMV) 感染与五种神经退行性疾病、脊髓性肌萎缩症 (SMA) 及相关综合征、帕金森病 (PD)、阿尔茨海默病 (AD)、多发性硬化症 (MS) 和神经系统疾病之间的关联。自主神经系统 (DANS)。该前瞻性队列包括 2006 年 1 月 1 日至 2021 年 12 月 31 日在英国生物银行接受 CMV 测试的英国白人。利用 Cox 比例风险模型来估计未来患五种神经退行性疾病的风险在有或没有 CMV 感染的个体中，根据模型 1 中的批次效应、年龄、性别和 Townsend 剥夺指数进行调整，并在模型 2 中另外针对 2 型糖尿病、癌症、骨质疏松症、维生素 D、单核细胞计数和白细胞计数进行调整。 双向孟德尔采用随机化方法验证 CMV 感染与 PD 之间的潜在因果关系。 共有 8346 名受试者，其中 4620 名女性（55.4%）和 3726 名男性（44.6%）为英国白人，平均年龄为 56.74 岁（8.11 岁），均被纳入本研究。结果显示，CMV感染并不影响患AD的风险（模型1：HR [95% CI] = 1.01 [0.57，1.81]，P = 0.965；模型2：HR = 1.00 [0.56，1.79]，P = 0.999），SMA 和相关综合征（模型 1：HR = 3.57 [0.64，19.80]，P = 0.146；模型 2：HR = 3.52 [0.63，19.61]，P = 0.152），MS（模型 1：HR = 1.16 [ 0.45，2.97]，P = 0.756；模型 2：HR = 1.16 [0.45，2.97]，P = 0.761）和 DANS（模型 1：HR = 0.65 [0.16，2.66]，P = 0.552；模型 2：HR = 0.65 [0.16，2.64]，P = 0.543）。有趣的是，我们发现，与血清阳性的参与者相比，CMV 血清阴性的参与者患 PD 的风险更高（模型 1：HR = 2.37 [1.25，4.51]，P = 0.009；模型 2：HR = 2.39 [1.25， 4.54]，P = 0.008）排除已故个体后。这种关联在男性中明显更强（模型 1：HR = 3.16 [1.42, 7.07]，P = 0.005；模型 2：HR = 3.41 [1.50, 7.71]，P = 0.003），但在女性中没有观察到显着差异子组（模型 1：HR = 1.28 [0.40, 4.07]，P = 0.679；模型 2：HR = 1.27 [0.40, 4.06]，P = 0.684）。然而，双向孟德尔随机分析并未发现 CMV 感染与 PD 之间存在遗传关联。研究发现，未感染 CMV 的男性患 PD 的风险较高。这些发现为帕金森病的危险因素提供了新的观点，并可能影响该疾病的公共卫生方法。国家自然科学基金 (81873776)、广东省自然科学基金 (2021A1515011681, 2023A1515010495)。© 2024作者。

Certain viral infections have been linked to the development of neurodegenerative diseases. This study aimed to investigate the association between cytomegalovirus (CMV) infection and five neurodegenerative diseases, spinal muscular atrophy (SMA) and related syndromes, Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and disorders of the autonomic nervous system (DANS).This prospective cohort included white British individuals who underwent CMV testing in the UK Biobank from January 1, 2006 to December 31, 2021. A Cox proportional hazard model was utilized to estimate the future risk of developing five neurodegenerative diseases in individuals with or without CMV infection, adjusted for batch effect, age, sex, and Townsend deprivation index in Model 1, and additionally for type 2 diabetes, cancer, osteoporosis, vitamin D, monocyte count and leukocyte count in Model 2. Bidirectional Mendelian randomization was employed to validate the potential causal relationship between CMV infection and PD.A total of 8346 individuals, consisting of 4620 females (55.4%) and 3726 males (44.6%) who were white British at an average age of 56.74 (8.11), were included in this study. The results showed that CMV infection did not affect the risk of developing AD (model 1: HR [95% CI] = 1.01 [0.57, 1.81], P = 0.965; model 2: HR = 1.00 [0.56, 1.79], P = 0.999), SMA and related syndromes (model 1: HR = 3.57 [0.64, 19.80], P = 0.146; model 2: HR = 3.52 [0.63, 19.61], P = 0.152), MS (model 1: HR = 1.16 [0.45, 2.97], P = 0.756; model 2: HR = 1.16 [0.45, 2.97], P = 0.761) and DANS (model 1: HR = 0.65 [0.16, 2.66], P = 0.552; model 2: HR = 0.65 [0.16, 2.64], P = 0.543). Interestingly, it was found that participants who were CMV seronegative had a higher risk of developing PD compared to those who were seropositive (model 1: HR = 2.37 [1.25, 4.51], P = 0.009; model 2: HR = 2.39 [1.25, 4.54], P = 0.008) after excluding deceased individuals. This association was notably stronger in males (model 1: HR = 3.16 [1.42, 7.07], P = 0.005; model 2: HR = 3.41 [1.50, 7.71], P = 0.003), but no significant difference was observed in the female subgroup (model 1: HR = 1.28 [0.40, 4.07], P = 0.679; model 2: HR = 1.27 [0.40, 4.06], P = 0.684). However, a bidirectional Mendelian randomization analysis did not find a genetic association between CMV infection and PD.The study found that males who did not have a CMV infection were at a higher risk of developing PD. The findings provided a new viewpoint on the risk factors for PD and may potentially influence public health approaches for the disease.National Natural Science Foundation of China (81873776), Natural Science Foundation of Guangdong Province, China (2021A1515011681, 2023A1515010495).© 2024 The Author(s).