巨细胞病毒感染与神经退行性疾病之间的关联:利用英国生物库数据建立的前瞻性队列。

IF 9.6 1区 医学 Q1 MEDICINE, GENERAL & INTERNAL EClinicalMedicine Pub Date : 2024-07-25 eCollection Date: 2024-08-01 DOI:10.1016/j.eclinm.2024.102757
Xuning Ma, Zijun Liao, Henghui Tan, Kaitao Wang, Cuilian Feng, Pengpeng Xing, Xiufen Zhang, Junjie Hua, Peixin Jiang, Sibo Peng, Hualiang Lin, Wen Liang, Xiaoya Gao
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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.</p><p><strong>Findings: </strong>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. 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This association was notably stronger in males (model 1: HR = 3.16 [1.42, 7.07], <i>P</i> = 0.005; model 2: HR = 3.41 [1.50, 7.71], <i>P</i> = 0.003), but no significant difference was observed in the female subgroup (model 1: HR = 1.28 [0.40, 4.07], <i>P</i> = 0.679; model 2: HR = 1.27 [0.40, 4.06], <i>P</i> = 0.684). However, a bidirectional Mendelian randomization analysis did not find a genetic association between CMV infection and PD.</p><p><strong>Interpretation: </strong>The study found that males who did not have a CMV infection were at a higher risk of developing PD. 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引用次数: 0

摘要

背景:某些病毒感染与神经退行性疾病的发生有关。本研究旨在调查巨细胞病毒(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)和自主神经系统疾病(DANS))之间的关联:该前瞻性队列包括 2006 年 1 月 1 日至 2021 年 12 月 31 日期间在英国生物库接受 CMV 检测的英国白人。利用 Cox 比例危险模型估算了感染或未感染 CMV 的个体未来罹患五种神经退行性疾病的风险,在模型 1 中对批次效应、年龄、性别和汤森贫困指数进行了调整,在模型 2 中对 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了额外调整。研究采用了双向孟德尔随机法来验证 CMV 感染与 PD 之间的潜在因果关系:本研究共纳入 8346 人,其中女性 4620 人(55.4%),男性 3726 人(44.6%),均为英国白人,平均年龄 56.74 岁(8.11)。结果显示,CMV 感染不影响罹患 AD(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 及相关综合征(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)、多发性硬化症(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,在排除死亡个体后发现,与血清反应阳性者相比,CMV血清反应阴性者患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)。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),但在女性亚组中未观察到显著差异(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:该研究发现,未感染 CMV 的男性罹患帕金森病的风险较高。研究结果为PD的风险因素提供了新的视角,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)。
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The association between cytomegalovirus infection and neurodegenerative diseases: a prospective cohort using UK Biobank data.

Background: 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).

Methods: 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.

Findings: 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.

Interpretation: 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.

Funding: National Natural Science Foundation of China (81873776), Natural Science Foundation of Guangdong Province, China (2021A1515011681, 2023A1515010495).

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来源期刊
EClinicalMedicine
EClinicalMedicine Medicine-Medicine (all)
CiteScore
18.90
自引率
1.30%
发文量
506
审稿时长
22 days
期刊介绍: eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
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