No genetic causal association between dental caries and Alzheimer's disease: a bidirectional two-sample Mendelian randomization analysis

Background: An increasing number of observational studies have suggested an association between dental caries and Alzheimer's disease (AD). The association between dental caries and Alzheimer's disease may be mediated by confounders or reverse causality. In this study, we conducted bidirectional two-sample Mendelian randomization (MR) to estimate the bidirectional causality between dental caries and AD.Materials and Methods: Genome-wide association study (GWAS) summary statistics of dental caries were extracted from a published meta-analysis which included a total of 487,823 participants. GWAS datasets of AD and AD onset age were obtained from the FinnGen bank. A bidirectional two-sample analysis was performed to explore the causality between dental caries and AD.Results: For the dental caries-AD causality estimation, there was no significant association between dental caries and AD, neither with the AD GWASs from the FinnGen database (OR: 1.041, p = 0.874) nor with those from the International Genomics of Alzheimer's Project (OR: 1.162, p = 0.409). In addition, the genetic susceptibility to dental caries was not related to the onset age of AD. No causality existed between dental caries and early-onset AD (OR: 0.515, p = 0.302) or late-onset AD (OR: 1.329, p = 0.347). For the AD-dental caries relationship, no causality was detected by the IVW method (OR: 1.000, p = 0.717). Findings from other MR methods were consistent. The pleiotropy test and sensitivity analysis confirmed the validity of these MR results. Conclusions: In this bidirectional MR study, robust evidence to support a bidirectional causal effect between dental caries and AD from the GWAS results within large-scale European-descent populations was absent. Having dental caries would not alter the onset age of AD.