站立身高与椎间盘退变因果关系的孟德尔随机化分析

The causal relationship between standing height and intervertebral disc degeneration:a mendelian randomization analysis

目的:探讨站立身高和椎间盘退变的因果关系。方法:从IEU OpenGWAS project数据库获取站立身高的全基因组关联研究(genome-wide association study,GWAS)数据集,筛选符合要求的单核苷酸多态性(single nucleotide polymorphism,SNP)位点作为工具变量;从FINNGEN数据库中获取关于椎间盘退变的GWAS数据集,从中筛选与工具变量匹配的SNP位点作为结局变量。将工具变量与结局变量导入分析工具R包,采用逆方差加权法(Inverse variance weighted,IVW)、MR-Egger回归、简单中位数法(Simple mode,SM)、加权中值法(Weighted median estimator,WME)、加权中位数法(Weighted mode,WM)进行孟德尔随机化(Mendelian randomization,MR)分析。采用MR-Egger截距检验、Cochran’s Q检验、留一法进行敏感性分析。结果:MR分析结果显示,站立身高与椎间盘退变呈正向因果关系[MR-Egger:OR=1.148,95%CI(0.942,1.401),P=0.174;WME:OR=1.220,95%CI(1.086,1.371),P=0.000;IVW:OR=1.113,95%CI(1.011,1.226),P=0.030;SM:OR=1.106,95%CI(0.837,1.462),P=0.479;WM:OR=1.234,95%CI(1.004,1.519),P=0.048]。MR-Egger截距检验结果表明,MR分析结果不存在水平多效性(P=0.726);异质性检验结果显示,站立身高SNP位点存在异质性(P=0.000);采用IVW的随机效应模型再次评估,结果显示站立身高与椎间盘退变呈正向因果关系(P=0.000),异质性存在对结果无影响;留一法检验结果显示,MR分析结果稳定。结论:站立身高与椎间盘退变呈正向因果关系。

Objective:To explore the causal relationship between standing height and intervertebral disc degeneration(IVDD).Methods:The genome-wide association study(GWAS)datasets about standing height was extracted from the IEU OpenGWAS project database,and the eligible single nucleotide polymorphism(SNP)loci were screened as instrumental variables;meanwhile,the GWAS datasets on IVDD was retrieved from the FINNGEN database,and the SNP loci matched with the instrumental variables were selected as the outcome variables.The instrumental variables and outcome variables were imported into an R package,and then a mendelian randomization(MR)analysis was conducted by using Inverse variance weighted(IVW),MR-Egger regression,Simple mode(SM),Weighted median estimator(WME)and Weighted mode(WM),and the sensitivity was examined via the MR-Egger intercept test,Cochran’s Q test,and the leave-one-out(LOO)test.Results:The results of MR analysis showed a positive causal relationship between standing height and IVDD(MR-Egger:OR=1.148,95%CI(0.942,1.401),P=0.174;WME:OR=1.220,95%CI(1.086,1.371),P=0.000;IVW:OR=1.113,95%CI(1.011,1.226),P=0.030;SM:OR=1.106,95%CI(0.837,1.462),P=0.479;WM:OR=1.234,95%CI(1.004,1.519),P=0.048).The results of MR-Egger intercept test indicated that there was no horizontal pleiotropy in the MR analysis results(P=0.726).The results of heterogeneity test revealed that there was heterogeneity in SNP loci of standing height(P=0.000).A re-evaluation was performed by employing a random-effects model of IVW,and the results showcased that the standing height had a positive causal relationship with IVDD(P=0.000),suggesting heterogeneity in SNP loci of standing height having no impact on the MR analysis results.Furthermore,the LOO test suggested that the results of MR analysis were stable.Conclusion:Standing height exhibits a positive causal relationship with IVDD.