Assessing the causal relationship between CRP, IL-1α, IL-1β, and IL-6 levels and intervertebral disc degeneration: a two-sample Mendelian randomization study

Growing research has suggested an association between chronic inflammation and Intervertebral disc degeneration (IVDD), but whether there is a causal effect remains unknown. This study adopted two-sample Mendelian randomization (MR) approach to explore the etiological role of chronic inflammation in IVDD risk. Here, summary statistics for C-reactive protein (CRP), interleukin (IL)-1 \(\mathcal {\alpha }\) $\alpha$ , IL-1 \(\mathcal {\beta }\) $\beta$ , IL-6 expression and IVDD were obtained from genome-wide association studies (GWAS) of European ancestry. MR analyses were conducted by using inverse variance weighted (IVW), Wald Ratio, weighted median, and MR-Egger method. Sensitivity analyses were conducted to assess the robustness of the results. The MR analyses suggested a lack of causal association of CRP, IL-6 , and IL-1 \(\mathcal {\alpha }\) $\alpha$ levels on IVDD (CRP-IVDD: odds ratio [OR] = 0.97, 95% confidence interval [CI] 0.86–1.09, P = 0.583; IL-6-IVDD: OR = 1.04, 95% CI 0.86–1.27, P = 0.679; IL-1 \(\mathcal {\alpha }\) $\alpha$ -IVDD: OR = 1.09, 95%CI 1.00–1.18, P = 0.058). However, there was a sign of a connection between genetically elevated IL-1 \(\mathcal {\beta }\) $\beta$ levels and a decreased IVDD incidence (OR = 0.87, 95%CI 0.77–0.99, P = 0.03). Our findings suggest a connection between IL-1 \(\mathcal {\beta }\) $\beta$ levels and the risk of IVDD. However, due to the support of only one SNP, heterogeneity and pleiotropy tests cannot be performed, the specific underlying mechanisms warrant further investigation.