Purpose <p>Humans are the only bipedal vertebrates, and the links between the lower-extremity muscles and spinal disorders have been highlighted. However, the exact relationships between them are not fully understood. This study aimed to elucidate the genetically predicted associations between lower-extremity muscle traits and spinal diseases using Mendelian randomization (MR) analysis.</p> Methods <p>We used summary statistics from genome-wide association studies for lower-extremity muscle traits from UK Biobank, including thigh muscle volume, thigh muscle fat infiltration, usual walking pace, etc.; and 31 types of spinal diseases from the FinnGen R10 to obtain genetic instrumental variables. We examined bidirectional MR evidence for causalities using inverse-variance weighted analyses and sensitivity analyses. A multivariate MR approach was applied to investigate the direct effect between the significant associations identified by univariate MR.</p> Results <p>Slow walking pace was found to be a risk factor associated with 10 spinal disorders. Low back pain and sciatica were two important risk factors genetically associated with the slower walking pace. In addition, higher posterior thigh muscle fat infiltration levels could significantly increase the odds of spinal stenosis, spondylolisthesis/spondylolysis, and spondylosis.</p> Conclusion <p>This MR study provides evidence of genetically predicted relationships between lower-extremity muscle traits and spinal diseases, and supports the development of lower-extremity exercise techniques for prevention and intervention of spinal disorders in clinical practice.</p>