Exploring causal correlations between inflammatory cytokines and intervertebral disc degeneration: A Mendelian randomization.

Abstract

Inflammatory cytokines have been reported to be related to intervertebral disc degeneration (IVDD) in several previous studies. However, it remains unclear about the causal relationship between inflammatory cytokines and IVDD. This study employs Mendelian randomization (MR) to analyze the causal link between inflammatory cytokines and the risk of IVDD. We used genetic variants associated with inflammatory cytokines from a meta-analysis of genome-wide association study (GWAS) in 8293 Finns as instrumental variables and IVDD data were sourced from the FinnGen consortium. The main analytical approach utilized Inverse-Variance Weighting (IVW) with random effects to assess the causal relationship. Additionally, complementary methods such as MR-Egger, weighted median, simple mode, weighted mode, and MR pleiotropy residual sum and outlier were employed to enhance the robustness of the final results. We found interferon-gamma (IFN-γ, <i>p</i> = 2.14 × 10-6, OR = 0.870, 95% CI = 0.821-0.921), interleukin-1 beta (IL-1b, <i>p</i> = 0.012, OR = 0.951, 95% CI = 0.914-0.989), interleukin-4 (IL-4, <i>p</i> = 0.034, OR = 0.946, 95% CI = 0.899-0.996), interleukin-18 (IL-18, <i>p</i> = 0.028, OR = 0.964, 95% CI = 0.934-0.996), granulocyte colony-stimulating factor (GCSF, <i>p</i> = 0.010, OR = 0.919, 95% CI = 0.861-0.980), and Stromal cell-derived factor 1a (SDF1a, <i>p</i> = 0.014, OR = 1.072, 95% CI = 1.014-1.134) were causally associated with risk of IVDD. Our MR analyses found a potential causal relationship between six inflammation cytokines (IFN-γ, IL-1b, IL-4, IL-18, SDF1a, and GCSF) and altered IVDD risk.