ArticleJournal of Crohn's & colitis2023
An Extremes of Phenotype Approach Confirms Significant Genetic Heterogeneity in Patients with Ulcerative Colitis.
Article in Journal of Crohn's & colitis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Genetic architecture of primary sclerosing cholangitis: shared pathways with inflammatory bowel disease and gut-liver axis mediation.International journal of surgery (London, England) · 2026Article
- Mucosally sourced complement factor B modulates the host response to colitis.bioRxiv : the preprint server for biology · 2026Article
- Pyroptosis in ulcerative colitis: biomarkers and therapeutic targets.Journal of biomedical science · 2025Review
- Genomic prediction with kinship-based multiple kernel learning produces hypothesis on the underlying inheritance mechanisms of phenotypic traits.Genome biology · 2025Article
- Optimizing 5-aminosalicylate for moderate ulcerative colitis: expert recommendations from the Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition.Intestinal research · 2025Review
- Evaluating genetic insights into ulcerative colitis and anxiety: Limitations and future directions.World journal of gastroenterology · 2024Article
- Large sample size and nonlinear sparse models outline epistatic effects in inflammatory bowel disease.Genome biology · 2023Article
- Analysis of the interferon-γ-induced secretome of intestinal endothelial cells: putative impact on epithelial barrier dysfunction in IBD.Frontiers in cell and developmental biology · 2023Article
Corrections and comments
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Authors and funding
20 authors at 13 institutions in 3 countries.
Funding
Abstract
BACKGROUND AND
aimsUlcerative colitis [UC] is a major form of inflammatory bowel disease globally. Phenotypic heterogeneity is defined by several variables including age of onset and disease extent. The genetics of disease severity remains poorly understood. To further investigate this, we performed a genome wide association [GWA] study using an extremes of phenotype strategy.
methodsWe conducted GWA analyses in 311 patients with medically refractory UC [MRUC], 287 with non-medically refractory UC [non-MRUC] and 583 controls. Odds ratios [ORs] were calculated for known risk variants comparing MRUC and non-MRUC, and controls.
resultsMRUC-control analysis had the greatest yield of genome-wide significant single nucleotide polymorphisms [SNPs] [2018], including lead SNP = rs111838972 [OR = 1.82, p = 6.28 × 10-9] near MMEL1 and a locus in the human leukocyte antigen [HLA] region [lead SNP = rs144717024, OR = 12.23, p = 1.7 × 10-19]. ORs for the lead SNPs were significantly higher in MRUC compared to non-MRUC [p < 9.0 × 10-6]. No SNPs reached significance in the non-MRUC-control analysis (top SNP, rs7680780 [OR 2.70, p = 5.56 × 10-8). We replicate findings for rs4151651 in the Complement Factor B [CFB] gene and demonstrate significant changes in CFB gene expression in active UC. Detailed HLA analyses support the strong associations with MHC II genes, particularly HLA-DQA1, HLA-DQB1 and HLA-DRB1 in MRUC.
conclusionsOur MRUC subgroup replicates multiple known UC risk variants in contrast to non-MRUC and demonstrates significant differences in effect sizes compared to those published. Non-MRUC cases demonstrate lower ORs similar to those published. Additional risk and prognostic loci may be identified by targeted recruitment of individuals with severe disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.