Assessing the causal relationship between genetically determined inflammatory biomarkers and low back pain risk: a bidirectional two-sample Mendelian randomization study

Abstract

Background: Observational studies have suggested an association between inflammatory markers and low back pain (LBP), but the causal relationship between these factors remains uncertain.

Methods: We conducted a bidirectional two-sample Mendelian randomization analysis (MR) study to investigate whether there is a causal relationship between inflammatory markers and low back pain. We obtained genetic data for CRP, along with its upstream inflammatory markers IL-6, IL-8, and IL-10, as well as low back pain from publicly available genome-wide association studies (GWAS). We applied several MR methods, including inverse variance weighting, weighted median, MR-Egger, Wald Ratio, and MR-PRESSO, to test for causal relationships. Sensitivity analyses were also conducted to assess the robustness of the results.

Results: Our analyses utilizing the Inverse Variance Weighted (IVW) method, the MR-Egger method, and the weighted median method indicated that IL-6 may be associated with an increased risk of LBP (Effect Size: -0.009, 95% Confidence Interval: -0.013-0.006, p = 9.16e-08); however, in the reverse direction, there was no significant causal effect of LBP on inflammatory markers.

Conclusion: Our study used a Mendelian randomization approach and found that elevated IL-6 levels may reduce the risk of LBP.

Keywords: Mendelian randomization; causality; inflammatory biomarkers; interleukin 6 (IL-6); low back pain.