Genetic evidence for the causal effects of malocclusion and dental attrition on temporomandibular disorders: A multivariable Mendelian randomization study.

STATEMENT OF PROBLEM: The causal role of occlusal factors, particularly malocclusion and dental attrition, in temporomandibular disorders (TMDs) remains unclear because of inconsistent observational evidence and confounding influences, limiting definitive conclusions regarding their independent etiological contributions.

PURPOSE: The purpose of this study was to investigate the independent causal effects of malocclusion and dental attrition on TMDs using multivariable Mendelian randomization (MVMR).

MATERIAL AND

METHODS

A 2-sample MR framework used genome-wide association study (GWAS) summary data from European cohorts. Pairwise Mendelian randomization (MR) analyses and linkage disequilibrium score regression (LDSC) estimated genetic correlations. MVMR then assessed independent causal effects, accounting for shared genetic architecture, utilizing the inverse variance weighted (IVW) method as the primary estimator. Instrument strength was verified via conditional F-statistics. Sensitivity analyses evaluated instrument heterogeneity (Cochran Q) and directional horizontal pleiotropy (MR-Egger intercepts).

RESULTS

Genetic liability to malocclusion demonstrated a strong association with TMD risk (IVW β=1.059, P<.001), remaining robust in MVMR (β=1.013, P≤.001). Conversely, dental attrition showed no causal effect (MVMR β=-.018, P=.078). LDSC revealed moderate genetic correlation (rg=.580). Sensitivity diagnostics confirmed the absence of heterogeneity and pleiotropy (P>.05).

CONCLUSIONS

Genetic liability to malocclusion was found to be an independent risk factor for TMDs, whereas attrition was found to be a secondary marker of occlusal instability, lacking an independent direct effect.