Potential causal association between serum vitamin D levels and intervertebral disc degeneration: A mendelian randomization study.

Objectives: Intervertebral disc degeneration (IDD) is a prevalent musculoskeletal disorder with substantial implications for disability and healthcare expenditures. The role of serum vitamin D (25-Hydroxyvitamin D, 25(OH)D) levels in the pathogenesis of various musculoskeletal conditions has been explored in prior observational studies, suggesting a potential association. While previous observational studies have suggested an association between the two conditions, it might confound the effect of 25(OH)D on IDD. This Mendelian randomization (MR) study seeks to elucidate the causal relationship between 25(OH)D and IDD.

Methods: We performed a MR analysis using summary-level data from genome-wide association studies (GWAS) of 25(OH)D (sample size = 441,291 European) and IDD (sample size = 336,439 (cases = 41,669, controls = 294,770) European). Single nucleotide polymorphisms (SNPs) significantly associated with 25(OH)D (p < 5 × 10^-8) were selected as instrumental variables. The associations between genetically predicted 25(OH)D and IDD were estimated using the inverse-variance weighted (IVW) method, with sensitivity analyses employing the weighted median, MR-Egger, and MR-PRESSO approaches to assess the robustness of the findings.

Results: In the primary IVW analysis, genetically predicted 25(OH)D was unrelated associated with IDD (odds ratio (OR) = 0.9671, 95% confidence interval (CI): 0.8956-1.0444, p = 0.39). The results remained consistent across the sensitivity analyses, and no significant directional pleiotropy was detected (MR-Egger intercept: p = 0.64).

Conclusions: This study found no obvious evidence that 25(OH)D is causally associated with IDD risks. We call for larger sample size studies to further unravel the potential causal relationship and the exact mechanism.