Graves' disease and inflammatory bowel disease: A bidirectional Mendelian randomization.

CONTEXT
Both Graves' disease (GD) and inflammatory bowel disease (IBD) are common autoimmune diseases that severely damage patients' quality of life. Previous epidemiological studies have suggested associations between GD and IBD. However, whether a causal relationship exists between these two diseases remains unknown.


OBJECTIVE
To infer a causal relationship between GD and IBD using bidirectional two-sample Mendelian randomization(MR).


METHODS
We performed bidirectional two-sample MR to infer a causal relationship between GD and IBD using GWAS summary data obtained from Biobank Japan (BBJ) and the International Inflammatory Bowel Disease Genetic Consortium (IIBDGC). Several methods (random-effect inverse variance weighted, weighted median, MR‒Egger regression, and MR-PRESSO) were used to ensure the robustness of the causal effect. Heterogeneity was measured based on Cochran's Q value. Horizontal pleiotropy was evaluated by MR‒Egger regression and leave-one-out analysis.


RESULTS
Genetically predicted IBD may increase the risk of GD by 24% (OR 1.24, 95% CI 1.01-1.52, p = 0.041). Crohn's disease (CD) may increase the risk of GD, whereas ulcerative colitis (UC) may prevent patients from developing GD. Conversely, genetically predicted GD may slightly increase the risk of CD, although evidence indicating that the presence of GD increased the risk of UC or IBD was lacking. Outlier-corrected results were consistent with raw causal estimates.


CONCLUSIONS
Our study revealed a potentially higher comorbidity rate for GD and CD. However, UC might represent a protective factor for GD. The underlying mechanism and potential common pathways await discovery.