Graves Disease and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization

Area of Science:

• Genetics
• Immunology
• Gastroenterology

Background:

• Graves disease (GD) and inflammatory bowel disease (IBD) are common autoimmune disorders impacting quality of life.
• Previous studies suggest an association between GD and IBD, but a causal link remains unestablished.

Purpose of the Study:

• To investigate the potential causal relationship between Graves disease and inflammatory bowel disease using bidirectional 2-sample Mendelian randomization.

Main Methods:

• Utilized genome-wide association study summary data from Biobank Japan and the International Inflammatory Bowel Disease Genetic Consortium.
• Employed multiple MR methods including inverse variance weighted, weighted median, MR-Egger, and MR-PRESSO for robust causal inference.
• Assessed heterogeneity with Cochran's Q and horizontal pleiotropy via MR-Egger regression and leave-one-out analysis.

Main Results:

• Genetically predicted IBD showed a 24% increased risk of GD (OR 1.24).
• Crohn's disease (CD) was associated with increased GD risk, while ulcerative colitis (UC) appeared protective against GD.
• GD showed a slight increase in CD risk, but no significant association with UC or overall IBD risk was found.

Conclusions:

• A potential comorbidity exists between Graves disease and Crohn's disease.
• Ulcerative colitis may confer a protective effect against Graves disease.
• The underlying mechanisms and shared pathways require further investigation.