代谢综合征与炎症性肠病的因果关系:两样本双向孟德尔随机化研究

Causal effect between metabolic syndrome and inflammatory bowel disease:a two-sample bidirectional Mendelian randomization study

目的采用孟德尔随机化(Mendelian randomization,MR)方法,探究代谢综合征(metabolic syndrome,MS)和炎症性肠病(inflammatory bowel disease,IBD)之间的双向因果关系。方法从MS全基因组关联研究数据中提取具有强相关的遗传变异作为工具变量,采用逆方差加权法、MR-Egger回归方法和加权中位数法估计MS和IBD发生风险的因果效应。结果逆方差加权法发现遗传预测的MS与IBD整体[OR=1.113,95%CI(1.020,1.216),P=0.017]和克罗恩病[OR=1.195,95%CI(1.072,1.333),P=0.001]的发生风险增加相关。反向MR分析发现溃疡性结肠炎与MS的发生风险降低存在关联[OR=0.969,95%CI(0.948,0.991),P=0.005]。结论基于MR分析结果表明,遗传预测的MS与IBD整体和克罗恩病的发生风险增加有关;溃疡性结肠炎与MS的发生风险降低有关。

Objective To investigate the bidirectional causal relationship between metabolic syndrome(MS)and inflammatory bowel disease(IBD)using Mendelian randomization(MR).Methods We extracted genetic variants with strong correlations from genome-wide association study data on MS as instrumental variables.Inverse variance weighting,MR-Egger regression methods,and weighted median methods were used to estimate the causal effect of MS and risk of developing IBD.Results Inverse variance weighting found that genetically predicted MS was associated with an increased risk of developing IBD overall(OR=1.113,95%CI 1.020 to 1.216,P=0.017)and Crohn's disease(OR=1.195,95%CI 1.072 to 1.333,P=0.001).And inverse MR analysis found ulcerative colitis was associated with a reduced risk of developing MS(OR=0.969,95%CI 0.948 to 0.991,P=0.005).Conclusion The results based on MR analysis suggest that genetically predicted MS is associated with the risk of IBD as a whole and Crohn's disease and ulcerative colitis are associated with a reduced risk of developing MS.