Assessment of Bidirectional Relationships Between Polycystic Ovary Syndrome and Periodontitis: Insights From a Mendelian Randomization Analysis

BACKGROUND: Observational studies have indicated an association between polycystic ovary syndrome (PCOS) and periodontitis, but it is unclear whether the association is cofounded or causal. We conducted a two-sample Mendelian randomization (MR) study to investigate the bidirectional relationship between genetically predicted PCOS and periodontitis. METHODS: From two genome-wide association studies we selected 13 and 7 single nucleotide polymorphisms associated with PCOS and periodontitis, respectively, as instrumental variables. We utilized publicly shared summary-level statistics from European-ancestry cohorts. To explore the causal effect of PCOS on periodontitis, 12,289 cases of periodontitis and 22,326 controls were incorporated, while 4,890 cases of PCOS and 20,405 controls in the reverse MR. Inverse-variance weighted method was employed in the primary MR analysis and multiple sensitivity analyses were implemented. RESULTS: Genetically determined PCOS was not causally associated with risk of periodontitis (odds ratio 0.97; 95% confidence interval 0.88–1.06; P = 0.50) per one-unit increase in the log-odds ratio of periodontitis. Similarly, no causal effect of periodontitis on PCOS was shown with the odds ratio for PCOS was 1.17 (95% confidence interval 0.91–1.49; P = 0.21) per one-unit increase in the log-odds ratio of periodontitis. Consistent results were yielded via additional MR methods. Sensitivity analyses demonstrated no presence of horizontal pleiotropy or heterogeneity. CONCLUSION: The bidirectional MR study couldn’t provide convincing evidence for the causal relationship between genetic liability to PCOS and periodontitis in the Europeans. Triangulating evidence across further observational and genetic-epidemiological studies is necessary.