Causal Relationship Between Systemic Circulatory Inflammatory Regulators and Intervertebral Disc Degeneration: A Bidirectional Two-Sample Mendelian Randomization Study

Abstract

Abstract Background In the context of the development of Intervertebral Disc Degeneration (IDD), inflammatory mediators play a pivotal role. Nevertheless, due to the influence of the inflammatory microenvironment, the causal relationship between specific inflammatory mediators and the development of IDD remains uncertain. Methods We utilized genetic data concerning systemic circulating inflammatory regulators obtained from a Genome-Wide Association Study (GWAS) analyzing 41 serum cytokines in a cohort of 8,293 individuals from Finland. The genetic data for IDD was derived from the most recent Genome-Wide Association Study summary statistics conducted within the FinnGen consortium, encompassing 37,636 IDD cases and 270,964 controls. Our analysis employed bidirectional two-sample Mendelian randomization (MR) techniques, which included several MR methods such as MR Egger, weighted median, inverse variance weighted (IVW), weighted mode, and simple mode. Additionally, the MR-PRESSO method was employed to identify horizontal pleiotropy, heterogeneity was quantified using the Cochran Q statistic, and MR Egger intercept analysis was performed to assess pleiotropy. Results We established causal relationships between three specific inflammatory factors and IDD. Elevated levels of MIP-1β [OR = 0.956, 95% CI: -0.08 to -0.006; P = 0.02] and IFN-G [OR = 0.915, 95% CI: -0.16 to -0.02; P = 0.01] expression were associated with a reduced risk of IDD. Conversely, genetic susceptibility to IDD was linked to a decrease in IL13 levels [OR = 0.967, 95% CI: -0.063 to -0.004; P = 0.03]. Conclusion In this study, we have identified inflammatory factors that exhibit a causal relationship with the onset and progression of IDD, as supported by genetic predictions.