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

## TL;DR

This study finds three blood metabolites that are genetically linked to causing pain in temporomandibular disorders.

## Contribution

The study identifies three metabolites with causal relationships to TMD-related pain using Mendelian randomization.

## Key findings

- Acetylcarnitine, Propionylcarnitine (c3), and X-24241 are significantly associated with TMD-related pain.
- Increased levels of these metabolites are causally linked to TMD-related pain.
- The findings suggest new therapeutic targets for TMD.

## Abstract

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.