Assessing the Causal Relationship Between CRP,IL-1α, IL-1β, and IL-6 Levels and Intervertebral Discdegeneration: a Two-Sample Mendelianrandomization Study

Abstract 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) approachto explore the etiological role of chronic inflammation in IVDD risk. Here, summary statistics for C-reactive protein (CRP),interleukin (IL)-1α, IL-1β, IL-6 expression and IVDD were obtained from genome-wide association studies (GWAS) of Europeanancestry. MR analyses were conducted by using inverse variance weighted (IVW), Wald Ratio, weighted median, and MR-Eggermethod. Sensitivity analyses were conducted to assess the robustness of the results. The MR analyses suggested a lackof causal association of CRP, IL-6 , and IL-1α 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-1α-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-1β levels and a decreased IVDDincidence(OR=0.87, 95%CI: 0.77-0.99, P=0.03). Our findings suggest a connection between IL-1β levels and the risk of IVDD.However, due to the support of only one SNP, heterogeneity and pleiotropy tests cannot be performed, the specific underlyingmechanisms warrant further investigation.