Deciphering genetic causality between inflammatory bowel disease and periodontitis through bi-directional two-sample Mendelian randomization

Abstract

Inflammatory bowel disease (IBD) and periodontitis are reported to be closely associated; however, whether there is a causal association between them remains unclear. To explore the existence of this causality, this study applied a bidirectional two-sample Mendelian randomization (MR). The genetic variants were obtained from the summary statistics of genome-wide association studies of IBD, including its subtypes CD and UC, and periodontitis. 175, 148, 113, and six single-nucleotide polymorphisms were selected as instrumental variables for IBD, CD, UC, and periodontitis, respectively. In MR analysis, random-effects inverse-variance weighted was used as the primary method, and weighted median and MR Egger regression were applied as the complementary method. A series of sensitivity analyses were also conducted to ensure the reliability of the results. None of these analyses found a significant effect of genetically proxied IBD and its subtypes on periodontitis, and vice versa. Subsequent sensitivity analyses did not detect any horizontal pleiotropy and heterogeneity. Caution should be exerted when it comes to clinical relevance and further studies are needed to clarify the relationship between IBD and periodontitis.