Alzheimer’s and Parkinson’s diseases in relation to human papillomavirus infection: A two-sample Mendelian randomization study

An increasing number of studies are exploring links between human papillomavirus (HPV) infection and neurodegenerative diseases. Yet, existing evidence from retrospective studies is prone to bias and cannot confirm causation. To address this, our 2-sample Mendelian randomization (MR) study utilizing single nucleoside polymers aims to establish a potential causal connection between HPV and the onset of Alzheimer disease (AD) and Parkinson disease (PD). We utilized a 2-sample MR approach to evaluate the causal relationships between HPV16 and HPV18 E7 proteins, HPV seropositivity, and the risks of AD and PD. Selected single nucleoside polymers from genome-wide association studies served as instrumental variables in HPV exposure data for MR analysis. Subsequent rigorous sensitivity assessments were also performed to ensure robustness. In this research, we explored the potential causal connections between HPV infection and the development of AD or PD through a MR analysis. Our findings suggest that the HPV18 E7 protein might act as a protective factor against PD, whereas HPV seropositivity was recognized as a risk factor for the same condition. Interestingly, neither the HPV16 E7 protein nor HPV seropositivity appeared to have any significant impact on the risk of AD. These findings shed light on HPV's intricate involvement in neurodegenerative diseases, offering fresh views on viral impacts on disorders like PD and AD. Recognizing study limitations, further research is crucial to confirm and clarify HPV's exact effects on these conditions.