Wenya Huang, Liyuan Xiao
Observational studies suggest an association between lichen planus (LP) and Alzheimer disease (AD), but causality remains unclear due to confounding and reverse causation. In this study, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis using Integrative Epidemiology Unit OpenGWAS database for LP (ID: finn-b-L12_LICHENPLANUS) and AD (ID: ebi-a-GCST90012877). The inverse-variance weighted (IVW) method was used as the primary analysis, complemented by MR-Egger, weighted median, simple mode, weighted mode, and sensitivity analyses to assess the robustness of the findings. Our analysis revealed a significant correlation between genetically predicted AD and an increased susceptibility to LP (P = .0001, odds ratio = 1.4326, 95% confidence interval = 1.1934-1.7196, IVW), providing genetic evidence supporting the oral-brain axis hypothesis. However, we did not detect any causal effect of genetic liability for LP on AD (P = .3749, odds ratio = 1.0147, 95% confidence interval = 0.9825-1.0476, IVW). This bidirectional MR study provides genetic evidence supporting a potential association between AD liability and increased susceptibility to LP, while no evidence was observed for an effect of LP on AD. These findings highlight the importance of further investigating immune-mediated mechanisms, including neuroinflammation and systemic immune dysregulation, that may connect neurodegenerative disorders with oral inflammatory diseases. Future studies are warranted to validate these findings and explore potential therapeutic implications.