Causal association between inflammatory bowel disease and IgA nephropathy: A bidirectional two-sample Mendelian...

Area of Science:

• Gastroenterology and Nephrology
• Genetic Epidemiology

Background:

• Observational studies suggest a link between inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), and IgA nephropathy (IgAN).
• The causal relationship between IBD and IgAN remains unclear.

Purpose of the Study:

• To investigate the causal relationship between IBD (UC and CD) and IgA nephropathy (IgAN).
• To clarify the directionality of the causal effect between these conditions using a two-sample Mendelian randomization analysis.

Main Methods:

• Utilized two-sample Mendelian randomization (MR) analysis with publicly available genome-wide association study (GWAS) summary statistics.
• Employed inverse-variance weighting (IVW), MR-Egger regression, MR-PRESSO, and weighted median methods.
• Assessed for horizontal pleiotropy and heterogeneity using MR-PRESSO, MR-Egger, Cochran's Q test, and leave-one-out analyses.

Main Results:

• Found significant positive causal effects of IBD (OR=1.58), UC (OR=1.55), and CD (OR=1.57) on the risk of IgAN.
• No significant horizontal pleiotropy or heterogeneity was detected, indicating robust and reliable results.
• No evidence for a causal effect of IgAN on IBD, UC, or CD was found.

Conclusions:

• Inflammatory bowel disease (IBD), including UC and CD, is causally associated with an increased risk of IgA nephropathy (IgAN).
• The study provides evidence supporting a unidirectional causal link from IBD to IgAN.
• Findings offer theoretical support for improved diagnosis and treatment strategies for patients with IBD and IgAN.