Herpesvirus infections and Alzheimer’s disease: a Mendelian randomization study

Springer Science and Business Media LLC - Tập 13 Số 1
Shu‐Yi Huang1, Yu‐Xiang Yang1, Kevin H.M. Kuo1, Hong‐Qi Li1, Xue‐Ning Shen1, Shi-Dong Chen1, Mei Cui1, Lan Tan2, Qiang Dong1, Jin‐Tai Yu1
1Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, Shanghai, 200040, China
2Department of Neurology, Qingdao Municipal Hospital, Qingdao University, 266071, Qingdao, China

Tóm tắt

AbstractBackgroundObservational studies have suggested that herpesvirus infection increased the risk of Alzheimer’s disease (AD), but it is unclear whether the association is causal. The aim of the present study is to evaluate the causal relationship between four herpesvirus infections and AD.MethodsWe performed a two-sample Mendelian randomization analysis to investigate association of four active herpesvirus infections with AD using summary statistics from genome-wide association studies. The four herpesvirus infections (i.e., chickenpox, shingles, cold sores, mononucleosis) are caused by varicella-zoster virus, herpes simplex virus type 1, and Epstein-Barr virus (EBV), respectively. A large summary statistics data from International Genomics of Alzheimer’s Project was used in primary analysis, including 21,982 AD cases and 41,944 controls. Validation was further performed using family history of AD data from UK Biobank (27,696 cases of maternal AD, 14,338 cases of paternal AD and 272,244 controls).ResultsWe found evidence of a significant association between mononucleosis (caused by EBV) and risk of AD after false discovery rates (FDR) correction (odds ratio [OR] = 1.634, 95% confidence interval [CI] = 1.092–2.446,P = 0.017, FDR-correctedP = 0.034). It has been verified in validation analysis that mononucleosis is also associated with family history of AD(OR [95% CI] = 1.392 [1.061, 1.826],P = 0.017). Genetically predicted shingles were associated with AD risk (OR [95% CI] = 0.867 [0.784, 0.958],P = 0.005, FDR-correctedP = 0.020), while genetically predicted chickenpox was suggestively associated with increased family history of AD (OR [95% CI] = 1.147 [1.007, 1.307],P = 0.039).ConclusionsOur findings provided evidence supporting a positive relationship between mononucleosis and AD, indicating a causal link between EBV infection and AD. Further elucidations of this association and underlying mechanisms are likely to identify feasible interventions to promote AD prevention.

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