Genetic prediction of blood metabolites and causal relationships with pain associated with temporomandibular disorders: a Mendelian randomization study.

BACKGROUND

This study aims to elucidate the causal relationships between 1400 blood metabolites and pain related to temporomandibular disorders (TMD) using Mendelian Randomization (MR) analysis.

METHODS

Utilizing data from genome-wide association studies (GWAS), our analysis was conducted with R software using the "TwoSampleMR" package. The primary method applied was Inverse Variance Weighted (IVW) analysis, which was supplemented with MR-Egger, Weighted Median, Simple Mode and Weighted Mode methods to examine the causal impact of blood metabolites on TMD-associated pain. We also assessed heterogeneity and the presence of horizontal pleiotropy using MR-Egger regression, MR-PRESSO (MR Pleiotropy Residual Sum and Outlier) global tests, and MR-Egger intercept tests.

RESULTS

Three metabolites-Acetylcarnitine, Propionylcarnitine (c3) and X-24241-were significantly associated with TMD-related pain. Specifically, Acetylcarnitine had an odds ratio (OR) of 1.409 (95% CI (confidence intervals): 1.016-1.954, p = 0.04), Propionylcarnitine (c3) had an OR of 1.194 (95% CI: 1.036-1.377, p = 0.014), and X-24241 had an OR of 1.408 (95% CI: 1.108-1.790, p = 0.005).

CONCLUSIONS

This study establishes a causal link between increased levels of these three metabolites and TMD-related pain. Our findings provide new insights into the pathogenesis of TMD and potential therapeutic targets.