Protective effects of sarcopenia-related traits on spinal degenerative diseases: A large prospective cohort study.

BACKGROUND: Paraspinal muscle degeneration has been implicated in the pathogenesis of spinal degenerative diseases. However, the impact of systemic muscle status, particularly sarcopenia, on SDD development remains poorly understood. METHODS: Multiple regression models, smooth curve fitting and threshold effect analyses were employed to evaluate associations between appendicular lean mass (ALM) and grip strength with SDDs using UK Biobank data (n = 490,116 for ALM; n = 497,300 for grip strength). Two-sample Using summary statistics from the UK Biobank and FinnGen consortium, the study performed Mendelian randomization (MR) analyses to assess causal relationships between sarcopenia-related traits (sample size ranging from 20,335 to 461,026) and four SDD phenotypes (sample size ranging from 6372 to 445,127). Finally, summary-data-based Mendelian randomization (SMR) analysis was performed to infer potential causal relationships between muscle expression quantitative trait loci (eQTLs) and SDDs. RESULTS: Observational analyses revealed significant nonlinear relationships and threshold effects between SDDs and both ALM and grip strength. In MR analyses, both WBLM and ALM exhibited protective causal effects against lumbar slipped discs and spinal stenosis, whereas no significant causal effect of grip strength on SDDs was detected. Further SMR analysis identified total of 12 genes (AAGAB, BTN2A2, and ABT1 emerged as statistical risk factors, while SNRNP27, SMAD3, PDXDC2P, CLEC18A, JAZF1, FAM53A, GKAP1, RP11-419C5.2, and RP11-20120.4 were identified as statistical protective factors) reaching significance (p < 0.05) across SDD outcomes. CONCLUSION: This study highlights that systemic muscle status, particularly muscle mass, may play a crucial role in SDDs progression, 12 genes with potential effects on SDDs, warranting further investigation.