Genetic prediction of 486 blood metabolites and their association with periodontitis risk:A mendelian randomization study

ZHAO Hong-yu; JIA Peng-lu; MA Ping; JIN Wu-long; HOU Shan-chun; YU Hua-jiao

doi:10.15956/j.cnki.chin.j.conserv.dent.2025.05.008

Abstract：AIM:This study aimed to investigatethe causal relationship between 486 blood metabolites and periodontitis using two-sample Mendelian randomization(MR)analysis,providing insights into potential biomarkers for the clinical management of periodontitis.METHODS:Two-sample MR was employed to assess the causal relationship between 486 blood metabolites and the risk of periodontitis.MR analysis was conducted using the TwoSampleMR package in R software.Multiple MR methods were applied,including inverse variance weighted(IVW),weighted median,MR-Egger,simple mode,and weighted mode,with IVW serving as the primary estimation method.Sensitivity analyses including MR-Egger intercept,MR-PRESSO,Cochran's Q statistic and leave-one-out analysis to assess potential heterogeneity and pleiotropy,ensuring the robustness of the results.RESULTS:Eleven metabolites were identified as significantly associated with periodontitis.Among these,8 metabolites,including 1,6-anhydroglucose,arabinose,quinate,creatine,X-13435,laurate,hydroquinone sulfate,and X-12063 exhibited positive association with the risk of periodontitis.Conversely,3 metabolites,including X-12231,X-04357,p-acetamidophenylglucuronide showed a negative association with periodontitis.Sensitivity analyses revealed no evidence of heterogeneity or pleiotropy,supporting the robustness of the findings.CONCLUSION:This MR study demonstrates a causal relationship between blood metabolites and periodontitis,identifying blood metabolites with both potential risk and protective effects.These findings contribute to the identification of novel periodontitis biomarkers and lay the foundation for a more comprehensive exploration of periodontitis mechanisms and potential therapeutic targets in the future.