Assessing the Causal Relationship Between Immune Cells and Temporomandibular Related Pain by Bi‑Directional Mendelian Randomization Analysis.

Introduction: Even with significant progress has been made in elucidating the pathogenesis of temporomandibular disorders (TMD), the pathophysiology of temporomandibular joint (TMJ) pain is still obscure. Our study aimed to explore whether there is a causal link between immune cells and TMD-related pain. Materials and Methods: Based on the TMD-related pain data obtained from the FinnGen Research Consortium and the 731 immune traits extracted from the GWAS Catalog and utilized a two sample Mendelian Randomization (MR) method, with immune cell as the exposure and TMD-related pain as the outcome. MR analyses were conducted employing the inverse-variance weighting method (IVW) as the primary analytical method to evaluate the causal association. Sensitivity analyses were conducted to enhance the robustness, heterogeneity and horizontal pleiotropy of the results. A reverse MR analysis was also conducted for immune cell traits identified in the initial MR analysis. Results: After false discovery rate (FDR) correction, two immune traits were observed and found to be significantly associated with TMD-related pain: Hematopoietic Stem Cell absolute count (OR=0.954, 95% CI= 0.933~0.976), and HLA DR+ CD4+ T cell (OR=1.040, 95% CI=1.019~1.061). On the reverse MR analysis, no significantly associated results were found in causal effects of TMD-related pain on immune traits. Conclusion: Our study showed a potential causal relationship between immune cells and TMD-related pain, eliminating reverse causality. These discoveries significantly enhance our knowledge of the interaction between immune traits and TMD-related pain, opening new possibilities for designing treatment from an immunological perspective.