A Genome-Wide Association Study Identifies IL23R as an Inflammatory Bowel Disease Gene
Open accessAbstract
The inflammatory bowel diseases Crohn's disease and ulcerative colitis are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. To identify genetic factors that might contribute to these disorders, we performed a genome-wide association study. We found a highly significant association between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23. An uncommon coding variant (rs11209026, c.1142G>A, p.Arg381Gln) confers strong protection against Crohn's disease, and additional noncoding IL23R variants are independently associated. Replication studies confirmed IL23R associations in independent cohorts of patients with Crohn's disease or ulcerative colitis. These results and previous studies on the proinflammatory role of IL-23 prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.
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Early genome-wide association wins in acute macular degeneration and inflammatory bowel disease were encouraging.
“Early wins in acute macular degeneration38 and inflammatory bowel disease39 were encouraging”
From A brief history of human disease genetics (2020) · cites this paper as [39]
Dermal γδ T cells respond to IL-23 and are a major source of IL-17A, IL-17F, and IL-22 in psoriatic lesions, contributing to disease pathogenesis.
“In addition to Th17 cells, dermal γδ T cells respond to IL-23 and are a major source of IL-17A, IL-17F, and IL-22 cytokines in psoriatic lesions, making them additional contributors to disease pathogenesis [120, 121].”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [120]
The IL-23-IL-17 axis is a critical driver of autoimmune disease, first in mouse models and later validated in humans by GWAS and clinical blockade.
“The so-called “IL-23-IL-17 axis” was found to function as a critical driver of autoimmune disease”
From The IL-17 Family of Cytokines in Health and Disease (2019) · cites this paper as Duerr et al., 2006
Some regions contain expected associations across diseases and traits; the association of the same common polymorphisms in IL23R in Crohn's disease, psoriasis, and ankylosing spondylitis points to a shared molecular cause.
“4) Some regions contain expected associations across diseases and traits. Crohn’s disease, psoriasis, and ankylosing spondylitis have long been recognized to share clinical features; the association of the same common polymorphisms in IL23R in all three diseases points to a shared molecular cause (96, 109, 110).”
From Genetic Mapping in Human Disease (2008) · cites this paper as [96]
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- Authors
- Duerr, R. H., Taylor, K. D., Brant, S. R., Rioux, J. D., Silverberg, M. S., Daly, M. J., Steinhart, A. H., Abraham, C., Regueiro, M., Griffiths, A., Dassopoulos, T., Bitton, A., Yang, H., Targan, S., Datta, L. W., Kistner, E. O., Schumm, L. P., Lee, A. T., Gregersen, P. K., Barmada, M. M., Rotter, J. I., Nicolae, D. L., & Cho, J. H.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Corresponding author
- Cho, Judy H.
- ORCID
- Duerr, Richard H.
- Taylor, Kent D.
- Brant, Steven R.
- Rioux, John D.
- Silverberg, Mark S.
- Daly, Mark J.
- Steinhart, A. Hillary
- Abraham, Clara
- Regueiro, Miguel
- Griffiths, Anne
- Dassopoulos, Themistocles
- Bitton, Alain
- Yang, Huiying
- Targan, Stephan
- Schumm, L. Philip
- Gregersen, Peter K.
- Barmada, M. Michael
- Rotter, Jerome I.
- Nicolae, Dan L.
- Cho, Judy H.
- Venue
- Science
- Published
- 2006-12
- Volume
- 314
- Issue
- 5804
- Pages
- 1461-1463
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4410764
- OpenAlex
- W1981714996
- Cited by
- 3,039
- References
- 30
- Citations by year
- 2026: 53 · 2025: 74 · 2024: 89 · 2023: 100 · 2022: 85 · 2021: 91 · 2020: 81 · 2019: 120 · 2018: 92 · 2017: 115 · 2016: 126 · 2015: 132 · 2014: 154 · 2013: 177 · 2012: 189
- FWCI
- 164.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK62432, DK62431, DK62423, DK62413, DK62422, DK62420, DK62429, U01DK062420, U01DK062429, U24DK062429, U01DK062413, U01DK062422, P30DK063491, U01DK062432, U01DK062431, U01DK062423)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- IL23R, Crohn's disease, ulcerative colitis, inflammatory bowel disease, genetic susceptibility, rs11209026, protective genetic variants, non-coding variants, therapeutic target
- MeSH terms
- Alleles, Chromosomes, Human, Pair 1, Colitis, Ulcerative, Crohn Disease, Genetic Markers, Genetic Testing, Haplotypes, Humans, Jews, Cohort Studies, Signal Transduction, Linkage Disequilibrium, Genome, Human, Case-Control Studies, Receptors, Interleukin, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Interleukin-23
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