Abstract: BACKGROUND: Observational studies have shown that intervertebral disc degeneration affects sedentary and physical activity levels; however, the causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration is unclear.
OBJECTIVE: To explore the causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration using the Mendelian randomization method.
METHODS: Five features associated with behavioral correlations in the Oswestry disability index score, including time spent watching TV, time spent on the computer, and light/moderate/vigorous physical activity, were selected from large-scale population-based genome-wide association studies, and instrumental variables were extracted for each of these behaviorally related features. Mendelian randomization analyses were performed in conjunction with the extraction of intervertebral disc degeneration as an outcome from the Finn Gen latest version 9 database. The results were analyzed using the inverse variance weighted, MR-Egger regression, simple mode, weighted mode, weighted median estimator, and regression model odds ratios (OR) and 95% confidence interval (CI) to assess the causal relationship between sedentary and physical activity levels in the Oswestry disability index scoring and intervertebral disc degeneration. Cochran’s Q was used to test for heterogeneity, MR-Egger intercept to test for multiplicity, and leave-one-out to test the sensitivity of single nucleotide polymorphisms to the causal relationship between exposure factors and disc degeneration.
RESULTS AND CONCLUSION: The results of the Mendelian randomization analysis using inverse variance weighted method showed a positive causal association between time spent watching TV/on the computer and the risk of intervertebral disc degeneration (OR=1.775, 95% CI: 1.418-2.221, P < 0.001)/(OR=1.384, 95% CI: 1.041-1.839, P < 0.001), an inverse causal association between light physical activity and the risk of intervertebral disc degeneration (OR=1.000, 95% CI: 0.999-1.000, P=0.020). MR-Egger intercept analysis indicated there was potential horizontal polytropy between light physical activity and intervertebral disc degeneration (P=0.005), while there was no horizontal pleiotropy between time spent watching TV, time spent on the computer and intervertebral disc degeneration (P=0.521, P=0.851). Cochran’s Q analysis showed that heterogeneity was observed between time spent watching TV, time spent on the computer and intervertebral disc degeneration (P=3.33×10-11, P=0.001), and no significant heterogeneity was observed between light physical activity and intervertebral disc degeneration (P=0.186). Overall, there is a bidirectional causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration, i.e., not only does intervertebral disc degeneration affect sedentary and physical activity levels in the Oswestry disability index score, but sedentary and physical activity levels in the Oswestry disability index score also affect intervertebral disc degeneration. These findings add to the genetic evidence for a positive effect of light physical activity on intervertebral disc degeneration, indicate that moderate/vigorous physical activity shows no significant causal relationship with intervertebral disc degeneration, and expand the evidence base for sedentary behaviors such as prolonged time spent watching TV/on the computer as a risk factor for intervertebral disc degeneration.

Key words: intervertebral disc degeneration, Oswestry disability index score, Mendelian randomization, causality, single nucleotide polymorphism, sedentary behavior, physical activity level