Deciphering genetic causality between inflammatory bowel disease and periodontitis: A Bidirectional Two-Sample Mendelian Randomization Analysis

Abstract Background: Inflammatory bowel disease (IBD) and periodontitis are closely associated; however, whether there is a causal association between them is unclear. To explore the existence of causation between genetically proxied inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and periodontitis, using a bidirectional two-sample Mendelian randomization analysis. Results: The genetic variants were obtained from the summary statistics of genome-wide association studies of IBD, CD, UC, and periodontitis. To investigate the potential causal association between genetic liability for IBD, including CD and UC, and periodontitis, we used random-effects inverse-variance weighted as primary method with weighted median, MR Egger regression as complementary methods, and a series of sensitivity analyses. Using 175, 148, and 113 single-nucleotide polymorphisms as instrumental variables for IBD, CD, and UC, respectively, we did not find a significant effect of genetically proxied IBD and its subtypes on periodontitis. Applying six single-nucleotide polymorphisms for periodontitis, we did not find a significant effect of the genetic liability for periodontitis on IBD, CD, and UC either. Sensitivity analyses did not reveal horizontal pleiotropy and heterogeneity. Conclusions: No causation in the forward or reverse direction was noted. Our resultssuggest that the treatment of one of these two conditions might not affect the other and help predict what future large-scale RCTs will show.