Abstract
INTRODUCTION AND AIMS: Observational studies suggest an association between metabolic syndrome (MetS) and periodontitis. However, observational studies are susceptible to reverse causation and confounding factors, so the causality of this association is uncertain. Causal association between compounds of MetS and periodontitis has been well studied. Using Mendelian randomisation (MR), we aimed to comprehensively evaluate the bidirectional relationship between MetS as a whole and periodontitis and provide clinical insight. METHODS: We used genetic instruments from the most comprehensive genome-wide association studies of European descent for MetS (n = 291,107) as well as periodontitis from both the FinnGen consortium (n = 195,395) and GeneLifestyle Interactions in Dental Endpoints (GLIDE, n = 45,563) consortium to investigate the causal relationship between MetS and periodontitis and vice versa. We used the inverse-variance weighted (IVW) method to derive the primary causal estimates and evaluated the robustness of our results with a series of sensitivity analyses. RESULTS: MR analysis based on FinnGen consortium indicated a negative causal association of MetS on periodontitis (OR = 0.882, 95% CI = 0.791-0.983, P = .023), while MR analysis based on GLIDE consortium did not support a causal relation of MetS on periodontitis (OR = 0.986, 95% CI = 0.920-1.057, P = .697). These results were consistent after adjusting for potential confounding factors by multivariable MR analyses. Results from meta analysis did not support a causal association of MetS on periodontitis. Sensitivity analysis showed that there was no existence of pleiotropy. In the reverse direction, periodontitis showed no association with MetS. CONCLUSIONS: Within the scope of this MR study, MetS and periodontitis are not causally related. CLINICAL RELEVANCE: Further studies are needed to clarify the underlying mechanism between metabolic syndrome and periodontitis.