阿片类药物使用与2型糖尿病因果关联的孟德尔随机化研究  

A Mendelian randomized study on the causal relationship between opioid use and type 2 diabetes mellitus

作　　者：薛茜 徐宁[1] 成浩[1] XUE Qian;XU Ning;CHENG Hao(Department of Anesthesiology,The First Affiliated Hospital of Soochow University,Suzhou 215006,China)

机构地区：[1]苏州大学附属第一医院麻醉科,江苏苏州215006

出　　处：《现代医学》2024年第12期1902-1909,共8页Modern Medical Journal

摘　　要：目的:基于双向孟德尔随机化方法探索阿片类药物使用与2型糖尿病(T2DM)之间的因果关联。方法:在IEU Open GWAS(https:∥gwas.mrcieu.ac.uk/)中获取阿片类药物使用与T2DM的数据进行全基因组关联分析。通过逆方差加权法(IVW)、MR-Egger回归、简单模式和加权中位数法(WM)进行两样本孟德尔随机化分析,并对结果采用多种敏感性分析进行校验。最后,采用反向孟德尔随机化分析验证结果的稳健性。结果:本研究纳入42个与阿片类药物使用强相关的单核苷酸多态性(SNPs)作为工具变量。4种方法的因果方向效应相同,结果均提示阿片类药物使用与T2DM之间呈正相关,不存在反向因果关联。其中IVW结果为OR=1.218(95%CI 1.094~1.356),P<0.001,MR-Egger回归、简单模式、WM的OR(95%CI)分别为1.056(0.774~1.440)、1.012(0.783~1.307)、1.079(0.974~1.196)。异质性检验结果P值<0.001,故应重点关注随机效应IVW模型。MR-Egger回归截距项接近0(Egger-intercept=-0.0016,P=0.685),即筛选出的SNPs不存在基因水平多效性。反向MR分析中未发现T2DM与阿片类药物使用上存在因果关联。结论:阿片类药物的使用会增加T2DM发生的风险。Objective:To study the causal relationship between opioid use and type 2 diabetes mellitus(T2DM)by two-sample Mendelian randomized analysis.Methods:The whole genomes of opioid use and T2DM were obtained from IEU Open GWAS(https:∥gwas.mrcieu.ac.uk/)database.Two-sample Mendelian randomized analysis was carried out using the inverse-variance weighted(IVW),MR-Egger regression,simple mode,and weighted median(WM),and the results were verified by multiple sensitivity analyses.Finally,reverse Mendelian randomization analysis was used to verify the robustness of the results.Results:The causal effects based on the four methods showed the same direction.The results all suggested that there was a positive causal correlation between BMI and anxiety,but there was no reverse causal correlation.The OR(95%CI)were 1.218(1.094-1.356),P<0.001,for IVW method,and 1.056(0.774~1.440),1.012(0.783~1.307),and 1.079(0.974~1.196)for MR-Egger regression,simple mode,and WM,respectively.The results of heterogeneity test were P<0.001,so we paid attention to the results of random effect IVW.The intercept of MR-Egger regression was close to 0(Egger-intercept=-0.0016,P=0.685),which indicated no pleiotropy for the selected SNPs.There is no causal correlation between T2DM and opioid use by reverse MR analysis.Conclusion:opioid use can increase the risk of T2DM.

关 键 词：阿片类药物 2型糖尿病 孟德尔随机化 因果关系 

分 类 号：R971.2[医药卫生—药品]