Abstract: 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.

Key words: intervertebral disc degeneration; sarcopenia; Mendelian randomization; causality