Abstract
BACKGROUND: Past studies have indicated links between specific inflammatory proteins in the bloodstream and temporomandibular disorders (TMDs). Nonetheless, there remains the need for further solid research pinpointing the exact causes behind these associations. This Mendelian randomization (MR) study aims to examine the association between 91 circulating inflammatory proteins and TMDs. METHODOLOGY: The most comprehensive genome-wide association studies available for circulating inflammatory proteins and TMDs was used in this two-sample MR analysis. The association between genetic predispositions to TMDs and levels of circulating inflammatory proteins was explored by various methods, including inverse variance weighted, MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO techniques. To evaluate the reliability of these findings, sensitivity analyses such as Cochran's Q test, the MR-Egger intercept test, and a leave-one-out approach were conducted. RESULTS: Findings indicated significant links between lower levels of circulating CCL4 (odds ratio, OR: 0.9241, 95% confidence interval, CI: 0.8679-0.984, p=0.0138), IL-20 (OR: 0.8615, 95%CI: 0.7566-0.9808, p=0.0243), and TWEAK (OR: 0.8702, 95%CI: 0.7634-0.992, p=0.0375) and an increased risk of TMDs, according to the inverse variance weighted method. Conversely, a higher level of S100A12 in the blood stream was associated with an increased risk of TMDs (OR: 1.1368, 95%CI: 1.0134-1.2752, p=0.0286). Sensitivity analyses confirmed the stability of these outcomes. CONCLUSION: This study suggests that reduced levels of CCL4, IL-20, and TWEAK are associated with a higher risk of TMDs, alongside an increased risk of TMDs connected to elevated levels of S100A12.