阿尔兹海默症和便秘:两样本双向孟德尔随机化研究

Alzheimer’s Disease and Constipation: A Two-Sample Bidirectional Mendelian Randomization Study

目的:采用双向两样本孟德尔随机化(MR)分析探讨阿尔茨海默病(Alzheimer’s Disease, AD)与便秘的因果关系,希望为临床防治提供理论依据。方法:使用公开的全基因组关联研究汇总数据集,运用逆方差加权法(IVW)、加权中位数法、MR-Egger回归法、简单模式(simple mode法)和加权模式(weighted mode法)进行两样本MR分析,评估AD与便秘的因果关系。结果:MR分析结果表明:AD与便秘增加存在正向因果关系(IVW: OR = 1.174, 95% CI: 1.068~1.290, P = 0.001),便秘与AD风险增加不存在因果关系(IVW: OR = 1.008, 95% CI: 0.977~1.039, P = 0.629)。在便秘对AD及其反向MR分析中,敏感性分析结果表明因果关系稳健,亦未检测到潜在的水平多效性。结论:两样本MR分析结果显示:AD与便秘风险增加存在正向因果关系,但便秘与AD风险增加不存在因果关系。

Objective: In this study, Mendelian randomization analysis (MR) was used to investigate whether Alzheimer’s disease (AD) and constipation are causal, thereby providing a theoretical foundation for clinical prevention and intervention of Alzheimer’s disease. Methods: In this study, Data for the two-sample Mendelian randomization study were obtained from public databases. Mendelian randomization analysis of the causal relationship between Alzheimer’s disease and constipation was performed using five regression models: random-effects Inverse-Variance Weighted (IVW), MR-Egger regression, simple mode, weighted mode and Weighted Median Estimator (WME). And inverse variance weighted (IVW) analysis was used as the main analysis. Results: IVW results found that AD was significantly related to the risk of constipation (IVW: OR = 1.174, 95% CI: 1.068~1.290, P = 0.001) and no evidence of the effect of constipation on the risk of AD (IVW: OR = 1.008, 95% CI: 0.977~1.039, P = 0.629). Tests for heterogeneity, pleiotropy, and sensitivity analyses showed that instrumental variables were not biased in the results. Conclusion: The study found a positive correlation between Alzheimer’s disease and constipation, while no correlation was observed between constipation and Alzheimer’s disease.