Causal Links Between Psychiatric Disorders, Sleep Apnea, and Oral and Maxillofacial Diseases Modules: A Mendelian Randomization Study

The impact of psychiatric disorders on oral/maxillofacial diseases through sleep apnea syndrome (SAS) remains incompletely understood. Using bidirectional and multivariable Mendelian randomization (MR), this study aimed to investigate potential causal links between psychiatric disorders, SAS, and oral/maxillofacial diseases, while assessing the mediating role of SAS. The authors analyzed genome-wide association study (GWAS) summary statistics using univariable MR to evaluate whether genetically predicted psychiatric disorders influence oral/maxillofacial manifestations; bidirectional MR and mediation MR were used to determine causal directionality and mediation effects. Univariable MR revealed that major depressive disorder increased risks of dentofacial anomalies (OR=1.25, 95% CI: 1.06-1.48, P =0.007), temporomandibular disorders (TMD) (OR=1.54, P =8×10 -5 ), and temporomandibular muscle pain (OR=1.52, P =0.0008); post-traumatic stress disorder elevated risks of dentofacial anomalies (OR=1.07, P =0.02) and TMD (OR=1.09, P =0.04); autism spectrum disorder was associated with temporomandibular muscle pain (OR=8.10, P =0.008). Bidirectional MR confirmed mutual causation between SAS and dentofacial anomalies. Mediation analysis estimated SAS mediated 21.5% (95% CI: 13.1%-31.2%) of the effect of major depressive disorder on dentofacial anomalies. Psychiatric disorders exert causal effects on oral/maxillofacial diseases, partially mediated by SAS; these results highlight SAS as a mediator between psychiatric disorders and oral/maxillofacial diseases and underscore its bidirectional causality with dentofacial anomalies, suggesting novel targets for preventive interventions.