Circulating VEGF and inflammatory bowel disease: a bidirectional mendelian randomization

Area of Science:

• Genetics
• Gastroenterology
• Immunology

Background:

• Observational studies suggest a link between vascular endothelial growth factor (VEGF) and inflammatory bowel disease (IBD).
• The directionality and causality of this association remain unclear.
• Inflammatory bowel disease encompasses Crohn's disease and ulcerative colitis.

Purpose of the Study:

• To investigate the causal relationship between circulating VEGF levels and IBD.
• To determine if VEGF influences Crohn's disease and ulcerative colitis risk.
• To assess potential reverse causality from IBD to VEGF.

Main Methods:

• Utilized summary data from genome-wide association studies (GWAS).
• Performed a two-sample bidirectional Mendelian randomization (MR) study.
• Conducted sensitivity analyses to confirm causal inference.

Main Results:

• A significant causal effect of circulating VEGF on Crohn's disease was identified (p < 0.013).
• No causal relationship was found between circulating VEGF and ulcerative colitis (p > 0.025).
• No evidence supported a reverse causal link from IBD to VEGF.

Conclusions:

• Circulating VEGF has a direct causal impact on the development of Crohn's disease.
• VEGF is unlikely to be a causal factor in ulcerative colitis.
• These findings clarify the etiological role of VEGF in IBD subtypes.