Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
PeerJ. 2023 Aug 23;11:e15936. doi: 10.7717/peerj.15936. eCollection 2023.
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.
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.
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, = 0.874) nor with those from the International Genomics of Alzheimer's Project (OR: 1.162, = 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, = 0.302) or late-onset AD (OR: 1.329, = 0.347). For the AD-dental caries relationship, no causality was detected by the IVW method (OR: 1.000, = 0.717). Findings from other MR methods were consistent. The pleiotropy test and sensitivity analysis confirmed the validity of these MR results.
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.
越来越多的观察性研究表明，龋齿与阿尔茨海默病（AD）之间存在关联。龋齿与阿尔茨海默病之间的关联可能受到混杂因素或反向因果关系的影响。在这项研究中，我们进行了双向两样本孟德尔随机化（MR）分析，以估计龋齿与 AD 之间的双向因果关系。
从一项包含 487823 名参与者的荟萃分析中提取了龋齿的全基因组关联研究（GWAS）汇总统计数据。AD 和 AD 发病年龄的 GWAS 数据集来自芬兰基因银行（FinnGen bank）。进行了双向两样本分析，以探讨龋齿与 AD 之间的因果关系。
对于龋齿与 AD 的因果关系估计，龋齿与 AD 之间没有显著关联，无论是与来自芬兰基因银行的 AD GWAS（OR：1.041， = 0.874）还是与国际阿尔茨海默病基因组学项目的 GWAS（OR：1.162， = 0.409）都没有关联。此外，龋齿的遗传易感性与 AD 的发病年龄无关。龋齿与早发性 AD（OR：0.515， = 0.302）或晚发性 AD（OR：1.329， = 0.347）之间不存在因果关系。对于 AD 与龋齿的关系，IVW 法没有检测到因果关系（OR：1.000， = 0.717）。其他 MR 方法的结果一致。多效性检验和敏感性分析证实了这些 MR 结果的有效性。
在这项双向 MR 研究中，在欧洲血统的大型人群中，基于 GWAS 结果的证据不足以支持龋齿与 AD 之间存在双向因果关系。患有龋齿不会改变 AD 的发病年龄。
