Inflammatory bowel disease and risk for hemorrhoids: a Mendelian randomization analysis

Observational studies have reported an association between inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), and hemorrhoids (HEM). However, the presence of a causal relationship within this observed association remains to be confirmed. Consequently, we utilized the Mendelian randomization (MR) method to assess the causal effects of IBD on hemorrhoids. We validated the association between IBD and hemorrhoids in humans based on genome-wide association studies (GWAS) data. To investigate the causal relationship between IBD and hemorrhoids, we performed a two-sample Mendelian randomization study using training and validation sets. The genetic variation data for IBD, CD, UC, and hemorrhoids were derived from published genome-wide association studies (GWAS) of individuals of European. Two-sample Mendelian randomization and Multivariable Mendelian randomization (MVMR) were employed to determine the causal relationship between IBD (CD or UC) and hemorrhoids. Genetically predicted overall IBD was positively associated with hemorrhoids risk, with ORs of 1.02 (95% CIs 1.01-1.03, P=4.39x10(-4)) and 1.02 (95% CIs 1.01-1.03, P=4.99x10(-5)) in the training and validation sets, respectively. Furthermore, we found that CD was positively associated with hemorrhoids risk, with ORs of 1.02 (95% CIs 1.01-1.03, P=4.12x10(-6)) and 1.02 (95% CIs 1.01-1.02, P=3.78x10(-5)) for CD in the training and validation sets, respectively. In addition, we found that UC in the training set was positively associated with hemorrhoids risk (ORs 1.02, 95% CIs 1.01-1.03, P=4.65x10(-3)), while no significant causal relationship between UC and hemorrhoids was shown in the validation set (P>0.05). However, after MVMR adjustment, UC in the training set was not associated with an increased risk of hemorrhoids. Our study showed that there is a causal relationship between CD and hemorrhoids, which may suggest that clinicians need to prevent the occurrence of hemorrhoids in CD patients.