A systematic analysis of IBD GWAS loci identifies most probable causal genes impacting intestinal epithelial functions

The study analyzed over 200 loci associated with inflammatory bowel disease (IBD) identified through genome-wide association studies. Researchers developed the IBD Priority Score to evaluate genes based on genetic, genomic, and functional data. This score identified a single gene in 71 of 104 regions containing multiple genes. Subsequently, they developed the Epithelial Priority Score, which identified 31 candidate genes relevant to intestinal epithelium. Functional studies on HT-29 cells demonstrated that the IRF6 gene enhanced antiviral responses, while the IRF8 gene suppressed them in intestinal epithelial cells stimulated with Poly(I:C). The results suggest that combining genetic, genomic, and functional data is an effective approach for identifying causal genes in IBD and for prioritizing functional validation studies.