Causal association between body mass index and temporomandibular disorders: a bidirectional two-sample Mendelian randomization analysis

Observational studies have shown that body mass index (BMI) is highly correlated with the occurrence of temporomandibular disorders (TMDs). However, these studies failed to present a causal relationship. Thus, we aimed to performed a Mendelian randomization (MR) study to investigate causality between BMI and TMDs. We performed a two-sample bidirectional MR analysis using large-scale genome-wide association studies (GWAS). Data were obtained from a large-scale BMI dataset (N = 322,154), TMDs dataset (N = 134,280). The causal effects were estimated with inverse-variance weighted (IVW) method, MR Egger, weighted median. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis and the funnel plot. In the forward MR analysis, a genetic prediction of low BMI was causally associated with a higher risk of TMDs (IVW OR: 0.575, 95% CI: 0.415-0.798, p: 0.001). Similar results were obtained using other complementary methods (MR Egger OR: 0.270, 95% CI: 0.104-0.698, p: 0.009; weighted median OR: 0.496, 95% CI: 0.298-0.826, p: 0.007). In the reverse MR results, TMDs was shown to have no significant effect on BMI (all p > 0.05). No pleiotropy and heterogeneity were detected in the bidirectional analysis (p > 0.05). A lower BMI might be causally associated with increased risk of TMDs, supporting the importance of weight control for the prevention of TMDs. Clinicians should pay more attention to the low-BMI patients among those seeking medical advice due to temporomandibular joint discomfort.