Associations Between Temporomandibular Disorders and Brain Imaging-Derived Phenotypes.

OBJECTIVE

Temporomandibular disorders (TMD) affect the temporomandibular joint and associated structures. Despite its prevalence and impact on quality of life, the underlying mechanisms of TMD remain unclear. Magnetic resonance imaging studies suggest brain abnormalities in patients with TMD. However, these lines of evidence are essentially observational and cannot infer a causal relationship. This study employs Mendelian randomisation (MR) to probe causal relationships between TMD and brain changes.

METHODS

Genome-wide association study (GWAS) summary statistics for TMD were collected, along with brain imaging-derived phenotypes (IDPs). Instrumental variables were selected from the GWAS summary statistics and used in bidirectional 2-sample MR analyses. The inverse-variance weighted analysis was chosen as the primary method. In addition, false discovery rate (FDR) correction of P value was used.

RESULTS

Eleven IDPs related to brain imaging alterations showed significant causal associations with TMD (P-FDR < .05), validated through sensitivity analysis. In forward MR, the mean thickness of left caudal middle frontal gyrus (OR, 0.76; 95% CI, 0.67-0.87; P-FDR = 1.15  ×  10-2) and the volume of right superior frontal gyrus (OR, 1.24; 95% CI, 1.10-1.39; P-FDR = 2.26  ×  10-2) exerted significant causal effects on TMD. In the reverse MR analysis, TMD exerted a significant causal effect on 9 IDPs, including the mean thickness of the left medial orbitofrontal cortex (β = -0.10; 95% CI, -0.13 to -0.08; P-FDR = 2.06 × 10-11), the volume of the left magnocellular nucleus (β = -0.15; 95% CI, -0.22 to -0.09; P-FDR = 3.26 × 10-4), the mean intensity of the right inferior-lateral ventricle (β = -0.09; 95% CI, -0.14 to -0.04; P-FDR = 2.23 × 10-2), the volume of grey matter in the anterior division of the left superior temporal gyrus (β = 0.09; 95% CI,  0.04-0.14; P-FDR = 1.69 × 10-2), and so forth.

CONCLUSIONS

This study provides genetic evidence supporting the bidirectional causal associations between TMD and brain IDPs, shedding light on potential neurobiological mechanisms underlying TMD development and its relationship with brain structure.