Periodontal disease increases the severity of chronic obstructive pulmonary disease: a Mendelian randomization study.

BACKGROUND: Recent research suggests that periodontitis can increase the risk of chronic obstructive pulmonary disease (COPD). In this study, we performed two-sample Mendelian randomization (MR) and investigated the causal effect of periodontitis (PD) on the genetic prediction of COPD. The study aimed to estimate how exposures affected outcomes. METHODS: Published data from the Gene-Lifestyle Interaction in the Dental Endpoints (GLIDE) Consortium's genome-wide association studies (GWAS) for periodontitis (17,353 cases and 28,210 controls) and COPD (16,488 cases and 169,688 controls) from European ancestry were utilized. This study employed a two-sample MR analysis approach and applied several complementary methods, including weighted median, inverse variance weighted (IVW), and MR-Egger regression. Multivariable Mendelian randomization (MVMR) analysis was further conducted to mitigate the influence of smoking on COPD. RESULTS: We chose five single-nucleotide polymorphisms (SNPs) as instrumental variables for periodontitis. A strong genetically predicted causal link between periodontitis and COPD, that is, periodontitis as an independent risk factor for COPD was detected. PD (OR = 1.102951, 95% CI: 1.005-1.211, p = 0.039) MR-Egger regression and weighted median analysis results were coincident with those of the IVW method. According to the sensitivity analysis, horizontal pleiotropy's effect on causal estimations seemed unlikely. However, reverse MR analysis revealed no significant genetic causal association between COPD and periodontitis. IVW (OR = 1.048 > 1, 95%CI: 0.973-1.128, p = 0.2082) MR Egger (OR = 0.826, 95%CI:0.658-1.037, p = 0.1104) and weighted median (OR = 1.043, 95%CI: 0.941-1.156, p = 0.4239). The results of multivariable Mendelian randomization (MVMR) analysis, after adjusting for the confounding effect of smoking, suggest a potential causal relationship between periodontitis and COPD (P = 0.035). CONCLUSION: In this study, periodontitis was found to be independent of COPD and a significant risk factor, providing new insights into periodontitis-mediated mechanisms underlying COPD development.

Genetic Predisposition to Periodontitis and Risk of Migraine: A Two-Sample Mendelian Randomization Study.

INTRODUCTION: Previous observational studies have associated periodontitis (PD) with migraine; however, the results are inconclusive and the causality of the association between PD and migraine remains unclear. This two-sample Mendelian randomization (MR) study was performed to explore the bi-directional causal relationship between PD and migraine. METHODS: To investigate the relationship between PD (17,353 cases; 28,210 controls) and migraine (1072 cases; 360,122 controls), we used genetic tools from the largest available genome-wide association study of European descent. Inverse variance-weighted (IVW) and a series of sensitivity analyses were used to explore the association between migraine and PD. We performed an MR study using seven SNPs (single nucleotide polymorphisms) as instrumental variables for PD to investigate the causal relationship between migraine and PD. RESULTS: We found no significant causal relationship between PD and migraine (odds ratio, OR = 1.000; 95% confidence interval, CI = 0.99-1.00; p = 0.65). Similarly, no evidence supported a causal relationship between migraine and PD (OR = 0.07; CI = 2.04 × 10-9-2.65 × 106; p = 0.77). A sensitivity analysis revealed that no potential polymorphic effect (p = 0.356) and heterogeneity (p = 0.652) exists for the variants used in constructing the genetic instrument. CONCLUSIONS: Based on the results of our MR study, there is no causal relationship between PD and migraines or migraines and PD.