Causal association between female reproductive factors and periodontitis: evidence from Mendelian randomization study.

OBJECTIVES: To evaluate the causal relationship between female reproductive factors and periodontitis, and identify potential mediators underlying these associations. MATERIALS AND METHODS: The genome-wide association study (GWAS) summary statistics from different consortiums was used to search for single nucleotide polymorphisms (SNPs) strongly associated with exposures as instrumental variables (IVs). The causality between female reproductive factors and periodontitis was measured by univariable mendelian randomization (UVMR). The mediation analysis was conducted by two-step mendelian randomization (Two-Step MR). The reverse MR was utilized to examine potential reverse causality. RESULTS: The age of menarche (beta 0.1328; 95%CI 0.0454-0.2203; p 0.0029) and the age of first birth (beta 0.1222; 95%CI 0.171-0.2247; p 0.0227) were positively correlated with chronic periodontitis. And the mediation analysis suggested that the heel bone mineral density (BMD) mediated the correlation between the age of menarche and chronic periodontitis. CONCLUSIONS: The age of menarche and the age of first birth have causal relationships with the infection risk of chronic periodontitis. Further clinical and laboratory researches are needed to clarify the mechanism behind the newly found causality. CLINICAL RELEVANCE: This study suggested that the later the age of menarche and first labor, the higher the susceptibility to chronic periodontitis, which may help the clinicians strengthen the prevention and treatment of periodontitis in women.