1型糖尿病与慢性阻塞性肺疾病的因果关系:一项双样本孟德尔随机化分析

Causal Relationship between Type 1 Diabetes Mellitus and Chronic Obstructive Pulmonary Disease:a Two-Sample Mendelian Randomization Analysis

目的基于双样本孟德尔随机化(MR)分析方法探讨1型糖尿病(T1DM)与慢性阻塞性肺疾病(COPD)的因果关系。方法T1DM、COPD数据集来自IEU OPEN GWAS,均为欧洲人,其中T1DM数据集样本量为24280例,单核苷酸多态性(SNP)为12783129个;COPD数据集样本量为462933例,SNP为9851867个。采用R 4.3.2软件中的TwoSampleMR包进行MR分析,其中逆方差加权法(IVW)为主要MR分析方法,MR-Egger回归、加权中位数法、简单模型、加权模型为次要MR分析方法。采用Cochran'sQ检验评估与T1DM强相关的SNP间的统计学异质性,采用MR-Egger回归的截距项评估与T1DM强相关的SNP的水平多效性,采用留一法分析单个SNP对MR分析结果的影响,采用漏斗图分析MR分析结果受潜在因素的影响。结果本研究最终筛选出14个与T1DM强相关的SNP。IVW分析结果显示,T1DM可增加COPD发生风险[OR=1.0003,95%CI(1.0001~1.0005),P<0.001];MR-Egger回归、加权中位数法、简单模型、加权模型分析结果亦显示,T1DM可增加COPD发生风险(P<0.05)。Cochran'sQ检验结果显示,与T1DM强相关的SNP间无统计学异质性(P>0.05);MR-Egger回归的截距项分析结果显示,与T1DM强相关的SNP不存在水平多效性(P>0.05);留一法分析结果显示,逐一剔除与T1DM强相关的SNP后,MR分析结果无明显改变。漏斗图分析结果显示,MR分析结果受潜在因素的影响较小。结论T1DM可增加COPD发生风险。

Objective To explore the causal relationship between type 1 diabetes mellitus(T1DM)and chronic obstructive pulmonary disease(COPD)by two-sample Mendelian randomization(MR)analysis.Methods The T1DM and COPD datasets were from IEU OPEN GWAS,all Europeans.The sample size of the T1DM dataset was 24280,and the number of single nucleotide polymorphisms(SNPs)was 12783129.The sample size of COPD dataset was 462933,and the number of SNPs was 9851867.MR analysis was performed using the TwoSampleMR package in R 4.3.2 software.The inverse-variance weighted(IVW)was the main MR analysis method,and the MR-Egger regression,weighted median method,simple model,and weighted model were secondary MR analysis methods.Cochran'sQtest was used to analyze the statistical heterogeneity among SNPs strongly associated with T1DM.The intercept term of MR-Egger regression was used to analyze the horizontal pleiotropy of SNPs strongly associated with T1DM.The effect of single SNP on MR analysis results was analyzed by leave-one-out method.Funnel plot was used to analyze the influence of potential factors on the results of MR analysis.Results Finally,14 SNPs highly associated with T1DM were included in this study.IVW analysis results showed that T1DM could increase the risk of COPD[OR=1.0003,95%CI(1.0001-1.0005),P<0.001].The results of MR-Egger regression,weighted median method,simple model and weighted model analysis also showed that T1DM could increase the risk of COPD(P<0.05).Cochran'sQtest results showed that there was no statistical heterogeneity among SNPs highly associated with T1DM(P>0.05).The results of intercept term of MR-Egger regression analysis showed that there was no horizontal pleiotropy in SNPs highly associated with T1DM(P>0.05).The results of leave-one-out analysis showed that there was no significant change in the results of MR analysis after eliminating the SNP highly associated with T1DM one by one.The results of funnel plot analysis showed that the results of MR analysis were less affected by potential factors.Conclusion T1DM can increase the risk of COPD.