Obstructive Sleep Apnea And Risk Of Maxillofacial Deformities,Periodontitis And Dental Caries: A Mendelian Randomized Study

Obstructive sleep apnea(OSA)is characterized by the repeated narrowing or collapse of the upper airway during sleep,leading to breathing interruptions.It is a complex condition influenced by various genetic and environmental factors,including craniofacial changes,obesity,and alterations in upper airway muscle function.The oral system plays a crucial role in OSA due to its direct involvement in the breathing process.Previous research has indicated a link between OSA and oral diseases such as craniofacial deformities,periodontitis,and dental caries,suggesting an association between the two.However,determining causality in conventional observational studies is challenging due to confounding factors like obesity and hypertension,as well as limitations such as residual confusion,reverse causality,and measurement errors.To strengthen causal inference,Mendelian randomization(MR)is utilized,which leverages natural genetic variations to mimic randomized controlled trials.By utilizing data from Genome-Wide Association Studies(GWAS)focused on OSA,maxillofacial deformities,periodontitis,and dental caries,we employed single-sample and twosample MR analysis to evaluate the potential causal relationships between OSA and periodontitis,dental caries,as well as five maxillofacial deformities(mandibular retraction,maxillary retraction,deep bite,overjet,and distal occlusion).This approach enables us to speculate on the causality of the disease and provide guidance for clinical treatment.Objective:The Mendelian randomized study was designed to investigate the causal relationship between OSA and oral diseases including maxillofacial deformities,periodontitis and dental caries,to verify the effect of maxillofacial deformities on OSA,and to explore the relationship between OSA and oral diseases.Methods:We used genetic variables from genome-wide association study abstracts of the Finn Gen and Gene-Lifestyle Interactions and Dental Endpoints(GLIDE)consortium to explore the causal relationship between OSA and oral diseases.Inverse variance weighted method,MR-Egger method,mode-based estimate method,and weighted median method were used to evaluate the primary causality.To assess the robustness of the results,the present study assessed horizontal pleiotropy by the MR-Egger intercept and MR-presso methods.Heterogeneity was assessed by the Cochran’ s Q test,and sensitivity was assessed by the leave-one-out method.Results:1.There was no causal relationship between OSA and oral diseases(dental caries,periodontitis)(P>0.05).OSA does not increase the risk of dental caries and periodontitis.2.There was no causality between OSA and dental malocclusion(deep bite,overjet,distal occlusion),nor was there reverse causality(P>0.05).OSA does not increase the risk of dental malocclusion,and dental malocclusion do not increase the risk of OSA.3.There is no bidirectional causality between OSA and maxillary retraction,but there is a bidirectional causality between OSA and mandibular retraction.OSA was associated with an increased risk of mandibular retraction [OR=2.18,(95%CI 1.56-3.06),P<0.01],and mandibular retraction was also associated with an increased risk of OSA [OR=1.06,(95%CI 1.02-1.09),P<0.01].4.Horizontal pleiotropy,heterogeneity,and sensitivity analyses indicated that the results of this study were reliable.Conclusion:1.There was no causal link between OSA and dental caries,periodontitis and dental malocclusion.2.There was a bidirectional causal relationship between OSA and mandibular retraction.3.This MR study offers limited evidence supporting a causal relationship between OSA and oral diseases,which introduces a novel concept and approach for the combined treatment of OSA and mandibular retraction.