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-现代医学

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

单位：苏州大学附属第一医院麻醉科, 江苏苏州 215006

分类号：R971.2

出版年·卷·期（页码）：2024·52·第十二期（1902-1909）

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=-0.001 6,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=-0.001 6, 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.

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