Atopic disease and inflammatory bowel disease: A bidirectional Mendelian randomization study

Area of Science:

• Genetics and Epidemiology
• Gastroenterology
• Immunology

Background:

• Observational studies suggest links between atopic diseases (allergic rhinitis, asthma, atopic dermatitis) and inflammatory bowel disease (IBD).
• The causal relationship between atopic diseases and IBD remains unclear.
• Mendelian randomization provides a robust method to investigate causality using genetic variants.

Purpose of the Study:

• To investigate the bidirectional causal relationships between allergic rhinitis (AR), asthma, atopic dermatitis (AD), and inflammatory bowel disease (IBD) subtypes (Crohn's disease [CD] and ulcerative colitis [UC]).
• To utilize two-sample Mendelian randomization (2SMR) to assess genetic evidence for causal links.
• To differentiate between atopic diseases causing IBD and IBD causing atopic diseases.

Main Methods:

• Pooled genome-wide association study (GWAS) data were used for instrumental variable selection.
• Two-sample Mendelian randomization (2SMR) analysis was performed to assess bidirectional causality.
• Instrumental variables were screened based on three core Mendelian randomization assumptions.

Main Results:

• Allergic rhinitis (AR) significantly increased the risk of CD, UC, and overall IBD.
• Asthma significantly increased the risk of CD, UC, and overall IBD, with a particularly strong association with CD.
• Atopic dermatitis (AD) showed a significant association with increased risk of CD and overall IBD.
• Reverse causality analysis indicated that CD significantly increased the risk of AR.

Conclusions:

• Atopic diseases, specifically AR and asthma, are causally linked to the development of IBD and its subtypes.
• AD is also causally associated with IBD, potentially mediated through CD.
• A bidirectional causal link exists, with CD increasing the risk for AR, highlighting complex interplay between these conditions.