Causal relationship of interferon-γ and interleukin-18 upstream of intervertebral disc degeneration pathogenesis: a two-sample Mendelian randomization study

Introduction: Intervertebral disc degeneration (IVDD) is a complex disease caused by genetic and environmental factors, but its pathogenesis is still unclear. Although studies of inflammatory cytokines have been used in recent years to unravel the biological mechanisms of a variety of diseases, such analyses have not yet been applied to IVDD. Therefore, we used a Mendelian Randomization approach to explore the potential mechanisms underlying the pathogenesis of IVDD. Methods: We obtained GWAS data from publicly available databases for inflammatory cytokines and IVDD, respectively, and explored the causal relationship between individual inflammatory cytokines and IVDD using instrumental variable (IV) analysis. We primarily used IVW methods to assess causality, while sensitivity, heterogeneity and multidirectionality analyses were performed for positive results (p < 0.05). All analyses were performed using R software. Results: In our study, we performed a two-sample MR analysis of 41 inflammatory cytokines to identify metabolites causally associated with IVDD. Ultimately, 2 serum metabolites associated with IVDD were identified (pval<0.05), IFN-gamma and IL-18. sensitivity, heterogeneity, and Pleiotropy test analyses were performed for all results. Conclusion: Our study identified a causal relationship between IFN-gamma and IL-18 and IVDD. It is valuable for the monitoring and prevention of IVDD and the exploration of targeted drugs. However, more evidence is needed to validate our study.