目的:探讨基础代谢率与椎间盘退变的因果关系。方法:分别从IEU OpenGWAS project数据库和FINNGEN数据库中筛选，获得基础代谢率的全基因组关联研究(genome-wide association study，GWAS)数据集和椎间盘退变的GWAS数据集。在分析工具R包中从基础代谢率的GWAS数据集中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，根据筛选出的工具变量从椎间盘退变数据集中匹配相应的SNP位点。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:纳入90个基础代谢率SNP位点作为工具变量。MR分析结果显示，基础代谢率与椎间盘退变呈负向因果关系[IVW:OR=0。69，95％CI(0。59，0。80)，P=0。000;WME:OR=0。69，95％CI(0。58，0。81)，P=0。000;MR-Egger:OR=0。59，95％CI(0。42，0。84)，P=0。004;WM:OR=0。59，95％CI(0。44，0。81)，P=0。001;SM:OR=0。91，95％CI(0。57，1。47)，P=0。710]。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。358)。异质性检验结果显示，基础代谢率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，结果显示基础代谢率与椎间盘退变呈负向因果关系(P=0。000)，异质性存在对结果无影响;留一法检验结果显示，无单个SNP位点对基础代谢率与椎间盘退变呈负向因果关系造成影响，MR分析结果稳定。结论:基础代谢率与椎间盘退变呈负向因果关系。
The causal relationship between basal metabolic rate and intervertebral disc degeneration:a mendelian ran-domization study
Objective:To explore the causal relationship between basal metabolic rate(BMR)and intervertebral disc degeneration(IVDD).Methods:The genome-wide association study(GWAS)datasets about BMR and IVDD were retrieved and extracted from the IEU OpenGWAS project database and FINNGEN database,respectively.Furthermore,the eligible single nucleotide polymorphism(SNP)loci were screened from the BMR GWAS datasets as the instrumental variables,and the SNP loci matched with the instrumental variables were selected from the IVDD GWAS datasets in the analysis tool R package.After that,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:Ninety BMR SNP loci were included and served as the instrumental variables.The results of MR analysis showed an inverse causal relation-ship between BMR and IVDD(IVW:OR=0.69,95％CI(0.59,0.80),P=0.000;WME:OR=0.69,95％CI(0.58,0.81),P=0.000;MR-Egger:OR=0.59,95％CI(0.42,0.84),P=0.004;WM:OR=0.59,95％CI(0.44,0.81),P=0.001;SM:OR=0.91,95％CI(0.57,1.47),P=0.710).The results of MR-Egger intercept test indicated that there was no horizontal pleiotropy in the MR analysis results(P=0.358).The results of heterogeneity test revealed that there was heterogeneity in SNP loci of BMR(P=0.000).A re-evaluation was per-formed by employing a random-effects model of IVW,and the results showcased that the BMR had an inverse causal relationship with IVDD(P=0.000),suggesting the heterogeneity in SNP loci of BMR having no impact on the MR analysis results.Furthermore,the LOO test showed that none of the single SNP loci had impact on the inverse causal relationship between BMR and IVDD,suggesting the results of MR analysis were stable.Conclusion:BMR exhibits an inverse causal relationship with IVDD.
intervertebral disc degenerationbasal metabolic rateMendelian randomization analysisgenome-wide association study
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