European Spine Journal - 2026-07-11 - Journal Article
Mapping the genetically predicted associations between lower-extremity muscle traits and spinal diseases.
Wang Q, Lu S
Topics
Key Takeaway
Mendelian randomization identifies slow walking pace as a genetically predicted risk factor for 10 spinal disorders, and higher posterior thigh muscle fat infiltration increases odds of spinal stenosis, spondylolisthesis/spondylolysis, and spondylosis.
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Summary
This bidirectional Mendelian randomization study used GWAS summary statistics from UK Biobank (muscle traits including thigh muscle volume, fat infiltration, walking pace) and FinnGen R10 (31 spinal disease categories) to test genetically predicted causal relationships. Slow walking pace was associated with 10 spinal disorders; low back pain and sciatica were in turn genetically associated with slower walking pace in the reverse direction. Higher posterior thigh muscle fat infiltration independently increased odds of spinal stenosis, spondylolisthesis/spondylolysis, and spondylosis on multivariate MR.
Key Limitation
Walking pace is a composite phenotype driven by pain, cardiopulmonary fitness, and neuromuscular function, making it impossible to attribute the observed associations specifically to muscle quality independent of pain behavior.
Original Abstract
PURPOSE
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.