炎症性肠病与消化道功能障碍性疾病的双向孟德尔随机化研究

Investigating Causal Relations between Inflammatory Bowel Disease and Digestive Tract Dysfunction Diseases: Bidirectional Mendelian Randomization Study

摘要: 目的：采用孟德尔随机化(MR)方法研究炎症性肠病和消化道功能障碍性疾病(胃食管反流病、功能性消化不良、贲门失弛缓症)的双向因果关系。方法：通过IEU数据库、芬兰数据库以及国际炎症性肠病遗传学联盟获得研究疾病的全基因组关联研究的汇总数据。本研究采用逆方差加权法(IVW)作为主要分析方法，MR-Egger、Weighted Median和Weighted Mode方法作为补充方法，以炎症性肠病为暴露因素，以三种消化道功能障碍性疾病为结局变量进行正向MR分析；以三种消化道功能障碍性疾病为暴露因素，以炎症性肠病为结局变量进行反向MR分析。使用Cochran’s Q检验评估异质性，MR-PRESSO和MR-Egger 截距评估水平多效性。结果：IVW法预测克罗恩病与功能性消化不良呈正向因果效应(OR = 1.04, 95%CI: 1.01~1.06, P = 0.003)，其余疾病的正反向分析均不存在因果效应。Cochran’s Q检验显示结果均不存在异质性(P > 0.05)。MR-PRESSO和MR-Egger截距显示结果均不存在水平多效性(P > 0.05)。结论：克罗恩病可能会增加功能性消化不良的风险。

Abstract: Objective: To study the bidirectional causality between inflammatory bowel disease and digestive tract dysfunction diseases (gastroesophageal reflux disease, functional dyspepsia, achalasia) using Mendelian randomization (MR) method. Methods: Aggregated data from Genome-Wide Association Studies were obtained from the IEU database, the FinnGen database, and the inflammatory bowel disease Genetics Consortium. This study used the inverse variance weighted (IVW) as the main analysis method, and the MR-Egger, Weighted Median and Weighted Mode methods as supplementary methods. Forward MR analysis was performed using inflammatory bowel disease as the exposure factor and three digestive tract dysfunction diseases as the outcome variables. Reverse MR analysis was performed using three digestive tract dysfunction diseases as exposure factors and inflammatory bowel disease as outcome variables. Heterogeneity was assessed using Cochran’s Q test, and horizontal pleiotropy was assessed using MR-PRESSO and MR-Egger intercept methods. Results: The IVW method predicted a positive causal effect between Crohn’s disease and functional dyspepsia (OR = 1.04, 95%CI: 1.01~1.06, P = 0.003). There was no causal effect in the forward and reverse analyses of other diseases. Cochran’s Q test showed that there was no heterogeneity in the results (P > 0.05). MR-PRESSO and MR-Egger intercept showed that there was no horizontal pleiotropy in the results (P > 0.05). Conclusion: Crohn’s disease may increase the risk of functional dyspepsia.