Journal of oral & facial pain and headache · 2025
Genetic prediction of blood metabolites and causal relationships with pain associated with temporomandibular disorders: a Mendelian randomization study.
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Zhang Xue'e, Le Ketong, Xi Weihong
Аннотация
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.
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.