Association between biological ageing and periodontitis: Evidence from a cross‐sectional survey and multi‐omics Mendelian randomization analysis

AIM: To investigate the relationship and potential causality between biological ageing and periodontitis. MATERIALS AND METHODS: We obtained the National Health and Nutrition Examination Survey (NHANES) and genome-wide association study (GWAS) summary statistics as well as single-cell sequencing data. Multivariate regression analysis based on cross-sectional data, Mendelian randomization (MR) and multi-omics integration analysis were employed to explore the causal association and potential molecular mechanisms between biological ageing and periodontitis. Additionally, two-step MR mediation analysis explored the risk factors in biological ageing-mediated periodontitis. RESULTS: We analysed data from 3189 participants in the NHANES data and found that higher biological age was associated with increased risk of periodontitis. MR analyses revealed causal associations between biological age measures and periodontitis risk. Frailty (odds ratio [OR] = 2.08, 95% confidence interval [CI]: 1.04-4.18, p = .039) and GrimAge acceleration (OR = 1.16, 95% CI: 1.01-1.32, p = .033) were causally associated with periodontitis risk, and these results were validated in a large-scale meta-periodontitis GWAS dataset. Additionally, the risk effects of body mass index, waist circumference and lifetime smoking on periodontitis were partially mediated by frailty and GrimAge acceleration. CONCLUSIONS: Evidence from cross-sectional survey and MR analysis suggests that biological ageing increases the risk of periodontitis. Additionally, improving the associated risk factors can help prevent both ageing and periodontitis.