Evaluating the bi-directional causal association between temporomandibular disorders and neurodegenerative diseases: a two-sample Mendelian randomisation study

Abstract Background Previous observational studies suggested that temporomandibular disorders (TMD) are associated with neurodegenerative diseases (NDs). This association may be mediated by confounding factors or reverse causation. Therefore, the objective of this study was to test the causal relationship between TMD and the four most common NDs [Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS)]. Methods Data on TMD (N = 134,280), AD (N = 63,926), PD (N = 482,730), ALS (N = 80,610), and MS (N = 115,803) were extracted from publicly available Genome-Wide Association Studies (GWAS). Single-nucleotide polymorphisms (SNPs) used as instrumental variables (IVs) were screened by setting the association strength and eliminating linkage disequilibrium. Inverse-variance weighting (IVW) method was employed as the primary analytical approach. However, weighted median, Mendelian randomization-Egger, and simple and weighted modes were used as complementary analysis methods to evaluate the causal effects. Tests for heterogeneity and pleiotropy were also performed. The results' stability was assessed using a leave-one-out analysis. Results Our findings revealed significant positive genetic correlations between TMD and PD (odds ratio = 1.223, 95% confidence interval = 1.064–1.406, P = 0.005). There was no significant association between TMD and AD, ALS, or MS. In the reverse Mendelian randomisation, no significant results supported the effect of NDs on TMD (all P > 0.05). The analyses did not reveal any evidence of heterogeneity or horizontal pleiotropy. Conclusions These results supply evidence of a potential causal relationship between TMD and PD, emphasising the importance of effectively managing TMD to prevent PD. However, it is imperative to conduct comprehensive studies to validate and elucidate the underlying mechanisms of this association.