Causal effect of infectious mononucleosis on neurodegenerative diseases: A Mendelian randomization study

Neurodegenerative diseases (NDs) are common chronic diseases with unknown etiology, and the association between virus and its pathogenesis is not clear. The aim of this study is to explore the role of virus in the pathogenesis of NDs by analyzing the causal effect between infectious mononucleosis (IM) mainly caused by Epstein-Barr virus and NDs. Based on the summary statistics of a large-scale genome-wide association study, we analyzed the causal effects of IM and NDs by Mendelian randomization (MR) using genetic variants as instrumental variables, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis. The reliability and stability of the MR analysis results were assessed by the MR-Egger intercept test, MR-PRESSO test, and heterogeneity test. Twenty-two single nucleotide polymorphisms that were significantly and strongly associated with IM were used as instrumental variables in the MR analysis. Inverse variance weighted as the main method of MR analysis shows that there were significant causal effects between IM and Alzheimer disease (OR: 1.037, 95% CI: 1.006-1.070) and Parkinson disease (OR: 0.964, 95% CI: 0.930-1.000), while IM was not significantly associated with amyotrophic lateral sclerosis (P = .269) and multiple sclerosis (P = .182). Sensitivity analyses showed that the results were robust. This study suggests that EB virus may contribute to the pathogenesis of NDs, and more research is needed to explore the specific mechanism of virus action on NDs.