Relationship Between Inflammatory Bowel Disease and Erythema Nodosum and Psoriasis: Using Mendelian Randomization

Abstract Background Erythema nodosum and psoriasis are two prevalent extraintestinal manifestations of inflammatory bowel disease (IBD). Erythema nodosum usually appears before or after the onset of IBD. Therefore, it has to be studied whether there is an association between erythema nodosum, psoriasis, and IBD, and their causal relationship remains to be explored. Methods To choose acceptable instruments, single nucleotide polymorphisms (SNPs) strongly associated with exposure, a series of quality control measures were used in our study. We utilized several robust analytical methods (inverse-variance weighted, weighted median, and MR-Egger regression) based on different assumptions of two-sample MR analysis to obtain more robust and reliable conclusions. To assess the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on erythema nodosum, MR-Egger intercept test, Cochran's test, and "leave-one-out" sensitivity analysis were performed. Results Our two-sample Mendelian randomized analysis, exposure GWAS aggregate, and GWAS aggregate results showed a positive association between IBD and erythema nodosum and psoriasis, consistent with many published observational studies, but our calculations revealed no statistical difference between the two. Conclusion MR estimations showed no significant association between inflammatory bowel disease and erythema nodosum (OR = 1.069; P > 0.05) and psoriasis (OR = 1.014; P > 0.05). Therefore, further research is required to understand better the relationship between IBD and erythema nodosum and psoriasis.