Association Between Periodontitis and Preeclampsia: A Bidirectional Mendelian Randomisation Analysis

Objectives: Studies have increasingly focussed on the relationship between periodontitis (PD) and preeclampsia (PE). However, conclusions have not been consistent, and it is unclear whether any causal relationship exists between them and whether causality is bidirectional. This study employed Mendelian randomisation (MR) analysis to investigate the potential bidirectional causal relationship between PD and PE. Methods: Genetic variants strongly linked to PD (17,353 cases and 28,210 controls), chronic periodontitis (CP; 1817 cases and 2215 controls), aggressive periodontitis (AgP; 851 cases and 6580 controls), and PE (7212 cases and 194,266 controls) in the genome-wide association study (GWAS) of European ancestry were used as instrumental variables (IVs). Inverse variance weighting (IVW) served as the primary method for causal inference. MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) was utilised to analyse horizontal pleiotropy. Cochrane Q tests and leave-one-out analyses were used to assess heterogeneity and stability amongst IVs. Results: The MR analysis revealed no causal impacts of PD or its 2 subtypes—CP and AgP—on PE. Similarly, no significant causal effect of PE on PD was found in the reverse-MR analysis (IVW odds ratio, 0.97; 95% confidence interval, 0.91–1.05; P = .58). The findings from MR–Egger, weighted median, weighted mode, and the simple modelling approaches, as well as the pleiotropy and sensitivity analyses, aligned with those of the IVW method. Conclusions: The MR analysis suggests no bidirectional causal relationship between PD and PE; hence, PD and PE might not increase or prevent the risk of one other. Clinical Relevance: Genetically, periodontitis or its subtypes chronic periodontitis and aggressive periodontitis may not require specific clinical attention to prevent the development of preeclampsia.