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Association between circulating inflammatory proteins and temporomandibular disorders: insight from a two-sample
Ao Ding1, Chan-Yuan Yu1, Feng Jiang2
1University of Science and Technology of China, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Department of Stomatology, Hefei, China.
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.
Insights
Lower levels of inflammatory proteins CCL4, IL-20, and TWEAK are linked to higher temporomandibular disorders (TMDs) risk. Conversely, elevated S100A12 protein levels are associated with increased TMD risk, according to Mendelian randomization analysis.
Area of Science:
- Genetics
- Immunology
- Oral and Maxillofacial Surgery
Background:
- Previous research suggests a connection between bloodstream inflammatory proteins and temporomandibular disorders (TMDs).
- Further investigation is needed to clarify the specific causal relationships underlying these associations.
- This study utilizes Mendelian randomization to explore links between 91 circulating inflammatory proteins and TMDs.
Purpose of the Study:
- To investigate the association between genetically predicted levels of 91 circulating inflammatory proteins and the risk of developing TMDs.
- To identify specific inflammatory biomarkers that may play a causal role in TMD pathogenesis.
- To leverage large-scale genetic data for robust causal inference in TMD research.
Main Methods:
- Employed a two-sample Mendelian randomization (MR) design using comprehensive genome-wide association study (GWAS) data for inflammatory proteins and TMDs.
- Utilized various MR methods including inverse variance weighted (IVW), MR-Egger, and weighted median to assess associations.
- Conducted sensitivity analyses (Cochran's Q, MR-Egger intercept, leave-one-out) to ensure the robustness and reliability of the findings.
Main Results:
- Inverse variance weighted analysis revealed that lower circulating levels of CCL4, IL-20, and TWEAK were significantly associated with an increased risk of TMDs.
- Elevated levels of the inflammatory protein S100A12 in the bloodstream were found to be associated with a higher risk of TMDs.
- Sensitivity analyses confirmed the stability and validity of these observed associations between specific inflammatory proteins and TMD risk.
Conclusions:
- Reduced circulating concentrations of CCL4, IL-20, and TWEAK are implicated as potential risk factors for TMDs.
- Increased circulating concentrations of S100A12 are associated with a heightened risk of developing TMDs.
- These findings highlight specific inflammatory proteins as potential targets for understanding and managing TMDs.
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