Interleukin-17 and inflammatory bowel disease: a 2-sample Mendelian randomization study.

Area of Science:

• Immunology
• Genetics
• Gastroenterology

Background:

• Observational studies suggest a complex relationship between interleukin-17 (IL-17) and inflammatory bowel disease (IBD).
• The precise causal role of individual IL-17 subtypes in IBD pathogenesis remains unclear.

Purpose of the Study:

• To investigate the causal associations between specific interleukin-17 (IL-17) subtypes and inflammatory bowel disease (IBD).
• To differentiate the effects of IL-17 subtypes on ulcerative colitis (UC) and Crohn's disease (CD).

Main Methods:

• Utilized a two-sample Mendelian randomization (MR) approach, employing both univariable and multivariable models.
• Performed rigorous sensitivity analyses to validate the robustness of the MR findings and assumptions.

Main Results:

• IL-17B, IL-17E, and IL-17RB demonstrated significant causal effects on increased ulcerative colitis (UC) risk.
• IL-17C and IL-17RC were causally associated with an elevated risk of Crohn's disease (CD).
• Multivariable MR indicated that IL-17B and IL-17E effects on UC were dependent on IL-17RB, while IL-17C and IL-17RC effects on CD were interdependent.

Conclusions:

• This study provides novel genetic evidence confirming causal links between specific IL-17 subtypes and IBD subtypes.
• Findings highlight distinct roles for IL-17 family members in UC and CD, warranting further mechanistic investigations.