{"title":"The association between cytomegalovirus infection and neurodegenerative diseases: a prospective cohort using UK Biobank data.","authors":"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","doi":"10.1016/j.eclinm.2024.102757","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</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. 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], <i>P</i> = 0.965; model 2: HR = 1.00 [0.56, 1.79], <i>P</i> = 0.999), SMA and related syndromes (model 1: HR = 3.57 [0.64, 19.80], <i>P</i> = 0.146; model 2: HR = 3.52 [0.63, 19.61], <i>P</i> = 0.152), MS (model 1: HR = 1.16 [0.45, 2.97], <i>P</i> = 0.756; model 2: HR = 1.16 [0.45, 2.97], <i>P</i> = 0.761) and DANS (model 1: HR = 0.65 [0.16, 2.66], <i>P</i> = 0.552; model 2: HR = 0.65 [0.16, 2.64], <i>P</i> = 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], <i>P</i> = 0.009; model 2: HR = 2.39 [1.25, 4.54], <i>P</i> = 0.008) after excluding deceased individuals. 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. The findings provided a new viewpoint on the risk factors for PD and may potentially influence public health approaches for the disease.</p><p><strong>Funding: </strong>National Natural Science Foundation of China (81873776), Natural Science Foundation of Guangdong Province, China (2021A1515011681, 2023A1515010495).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"74 ","pages":"102757"},"PeriodicalIF":9.6000,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327475/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"EClinicalMedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.eclinm.2024.102757","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
Abstract
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).
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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