Immune-mediated inflammatory diseases and periodontal disease: a bidirectional two-sample mendelian randomization study.

ABSTRACT

BACKGROUND: Previous observational studies have shown a bidirectional association between immune-mediated inflammatory disorders (IMID) and periodontal disease. However, evidence regarding the causal role of IMID and periodontal disease is still lacking. Therefore, we conducted a bidirectional two-sample Mendelian randomization (MR) study to uncover the potential genetic causal effects between IMID and periodontal disease. METHODS: Bidirectional two-sample MR analysis was employed. Data for ten IMIDs were sourced from genome-wide association studies (GWAS) conducted by the FinnGen Consortium (range from 1023 to 36321 cases) and UK Biobank (UKB) (range from 150 to 17574 cases). Furthermore, GWAS data for periodontal disease were obtained from the FinnGen Consortium (87497 cases), UKB (458 cases), and Gene Lifestyle Interactions in Dental Endpoints (GLIDE) consortium (17,353 periodontitis cases). Subsequently, the causal relationships were analyzed by random effects inverse variance weighting, weighted median, and MR-Egger. Sensitivity analyses were performed using the Cochrane Q test, funnel plot, and Mr-Egger intercept test to ensure robustness. Eventually, replication analysis and meta-analysis across different databases were carried out. RESULTS: Systemic lupus erythematosus (SLE) [IVW OR = 1.079 (95% CI 1.032-1.128) and P < 0.001], Sjogren syndrome [IVW OR = 1.082 (95% CI 1.012-1.157) and P = 0.022] and hypothyroidism [IVW OR = 1.52 (95% CI 1.13-2.04) and P = 0.005] may increase the risk of periodontal disease. In addition, periodontal disease may reduce the risk of SLE [IVW OR = 0.8079 (95% CI 0.6764-0.9650) and P = 0.019] and hyperthyroidism [IVW OR = 5.59*10-9 (95% CI 1.43*10-15-2.18*10-2) and P = 0.014]. Meta-analysis indicated a causal correlation between SLE and an increased risk of periodontal disease [OR = 1.08 (95% CI 1.03-1.13), P = 0.0009]. No significant evidence suggests bilateral causal relationships between other IMIDs and periodontal disease. No significant estimation of heterogeneity or pleiotropy is detected. CONCLUSIONS: Our study has confirmed a genetic causal relationship between IMIDs and periodontal disease, thereby unveiling novel potential mechanisms underlying IMIDs and periodontal disease. This discovery is promising in fostering interdisciplinary collaboration between clinicians and stomatologists to facilitate appropriate and precise screening, prevention, and early treatment of IMIDs and periodontal disease.