肌肉质量增加可能导致椎间盘退变:一项两样本孟德尔随机化研究

Increased muscle mass increases risks of intervertebral disc degeneration:a two-sample Mendelian randomization study

目的采用两样本孟德尔随机化分析方法研究肌肉减少症(SP)与椎间盘退变(IVDD)之间的因果关系。方法获取SP(肌肉瘦体质量、左右手握力)和IVDD的全基因组关联研究数据库,并得到与暴露强相关单核苷酸多态性(SNP)作为工具变量。保守去除吸烟、久坐两个混杂因素,通过逆方差加权法(IVW)、加权中位数法、MR-Egger法进行孟德尔随机化分析来评估SP和IVDD的因果关系。通过MR-PRESSO、双重验证、阴性对照、异质性和多样性检验来确保结果的一致性和准确性。结果有570、97、79个分别与肌肉瘦体质量、左右手握力强相关的SNP被纳入分析,结果显示肌肉瘦体质量和IVDD显著正相关(IVW:OR=1.139,95%CI=(1.076,1.204),P=6.619e-6),和右手握力可能存在正相关关系。在MR-PRESSO和选择新的IVDD数据库重新分析后结果与之前基本保持一致。结论肌肉质量增加可能提高椎间盘退变的风险。

Objective To investigate the causal relationship between sarcopenia(SP)and intervertebral disc degeneration(IVDD)using two-sample Mendelian randomization analysis.Methods Genome-wide association study(GWAS)databases of SP(lean body mass,right and left hand grip strength)and IVDD were obtained.The single nucleotide polymorphisms(SNPs)strongly associated with exposure were obtained as an instrumental variable.After conservatively removing two confounders(smoking and sedentary life style),the causal relationship between SP and IVDD was assessed using Mendelian randomization analyses through the inverse variance weighting(IVW),weighted median(WM)and MR-Egger methods.The consistency and accuracy of the results were verified by MR-PRESSO,double validation,negative control,heterogeneity and diversity tests.Results A total of 570 SNPs associated with lean muscle mass,97 with strong right hand grip strength,and 79 with strong left hand grip strength were included in the analysis.The results showed that lean muscle mass had a significant positive correlation with IVDD(IVW:OR=1.139,95%CI:1.076-1.204,P=6.619e-6)and right hand grip strength had a possible positive correlation with IVDD.After reanalysis in MR-PRESSO and selection of a new IVDD database,the results remained largely consistent with the previous results.Conclusion Increased muscle mass may increase the risk of intervertebral disc degeneration.