Causal Association of Inflammatory Bowel Disease on Anorexia Nervosa: a Two-Sample Mendelian Randomization Study

Abstract

Anorexia nervosa (AN) is a severe and complex psychiatric disorder with the highest mortality rate of all psychiatric disorders. Previous observational studies indicated inconclusive association between inflammatory bowel disease (IBD) and AN, and the causal effect remains unclear. We aimed to test the hypothesis that a causal relationship exists between IBD and the risk of AN using the bi-directional two-sample Mendelian randomization (MR) analysis. The inverse-variance weighted (IVW) method was employed as the primary analysis. Furthermore, various sensitivity analyses were conducted to assess the robustness of our results. Notably, IVW analysis of univariable MR revealed that genetically predicted IBD were significantly casually associated with AN risk. In subgroups, consistent positive causal associations with AN might show in ulcerative colitis (UC) and Crohn’s disease (CD). Besides, there was no heterogeneity and horizontal pleiotropy observed in the sensitivity analysis. Our study identifies that genetic susceptibility to IBD (NSNP = 12, odds ratio [OR]: 1.143, 95% CI: 1.032–1.266, P = 0.01), including UC (NSNP = 6, OR: 1.153, 95% CI: 1.022–1.301, P = 0.021) and CD (NSNP = 4, OR: 1.153, 95% CI: 1.008–1.319, P = 0.037), could be causally associated with an increased risk of AN. No evidence was observed on the causal effect of AN on IBD, including UC and CD. Our findings may have clinical benefits for early detection of AN and clinical decisions on management of IBD patients.