Association between inflammatory bowel disease and interleukins, chemokines: a two-sample bidirectional mendelian...

Area of Science:

• Immunology
• Genetics
• Gastroenterology

Background:

• Investigating the causal links between inflammatory bowel disease (IBD) and immune mediators like interleukins (ILs) and chemokines is crucial for understanding disease pathogenesis.
• Mendelian randomization (MR) offers a robust approach to explore these bidirectional relationships using genetic data.

Purpose of the Study:

• To determine the causal effect of specific interleukins (ILs) and chemokines on the risk of developing inflammatory bowel disease (IBD).
• To investigate whether IBD and its subtypes, ulcerative colitis (UC) and Crohn's disease (CD), causally influence the circulating levels of ILs and chemokines.

Main Methods:

• Utilized Mendelian randomization (MR) with genetic summary data from large genome-wide association studies.
• Employed inverse variance weighting (IVW) as the primary analysis method, supplemented by MR-Egger and weighted median approaches for robustness.
• Conducted sensitivity analyses to assess heterogeneity and horizontal pleiotropy, ensuring the reliability of causal inference.

Main Results:

• Genetically predicted levels of IL-16, IL-18, and CXCL10 showed a significant positive causal association with IBD risk.
• IL-12p70 and CCL23 exhibited a significant negative causal association with IBD.
• Suggestive evidence indicated IL-16 and IL-18 may increase UC risk, while CXCL10 may increase CD risk.
• No significant causal evidence was found for IBD or its subtypes influencing IL or chemokine levels.

Conclusions:

• Specific interleukins (ILs) and chemokines play a causal role in the development of inflammatory bowel disease (IBD).
• Conversely, IBD and its major subtypes (UC and CD) do not appear to causally affect the circulating levels of these immune molecules.