Causal association between systemic diseases and periodontitis: a two-way two-sample Mendelian randomization study.

Area of Science:

• Genetics and Public Health
• Oral and Systemic Disease Epidemiology

Background:

• The relationship between systemic diseases and periodontitis is complex and potentially bidirectional.
• Confounding factors often obscure the true causal links between oral health and systemic conditions.

Purpose of the Study:

• To investigate the causal relationship between various systemic diseases and periodontitis using a bidirectional two-sample Mendelian randomization (MR) approach.
• To explore whether periodontitis causally influences the risk of developing specific systemic diseases.

Main Methods:

• Utilized genome-wide association study (GWAS) summary statistics from large consortia (IEU OpenGWAS, FinnGen, GLIDE).
• Employed inverse-variance weighted (IVW) MR as the primary method, supported by MR-Egger, weighted median, and weighted mode analyses.
• Conducted sensitivity analyses (MR-PRESSO, MR-Egger intercept, Cochran's Q) to ensure result robustness and detect pleiotropy.

Main Results:

• Forward MR analysis found no significant causal effect of genetic liability to selected systemic diseases on periodontitis risk.
• Reverse MR analysis revealed a significant causal link: periodontitis is a risk factor for osteoporosis (OR 1.16, P=0.031).
• Sensitivity analyses confirmed the robustness of the periodontitis-osteoporosis association, with no significant horizontal pleiotropy detected.

Conclusions:

• This study provides novel evidence that periodontitis may causally increase the risk of osteoporosis.
• Findings underscore the systemic implications of oral health and suggest periodontitis management as a potential osteoporosis prevention strategy.
• Recommends integrating periodontal screening into osteoporosis risk assessment for enhanced early intervention and multidisciplinary care.