Phenotype-Stratified Genetic Linkage Study Demonstrates that IBD2 Is an Extensive Ulcerative Colitis Locus View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-03

AUTHORS

A Hillary Steinhart, Anne M Griffiths, Dan L Nicolae, Deepa Reddy, Gillian P Bromfield, Huiying Yang, Jean-Paul Achkar, Jeffrey A Tuvlin, John D Rioux, Judy H Cho, Kathy Siminovitch, Leilei Zhang, Lisa W Datta, M Michael Barmada, Mark S Silverberg, Phil Schumm, Richard H Duerr, Robin S McLeod, Stephen B Hanauer, Steven R Brant, Themistocles Dassopoulos, Theodore M Bayless, Zane Cohen

ABSTRACT

OBJECTIVES: The complete elucidation of genetic variants that contribute to inflammatory bowel disease (IBD) will likely include variants that increase risk to both Crohn's disease and ulcerative colitis as well as variants that increase risk for particular phenotypic subsets. The purpose of this study was to assess phenotypic subsets that contribute to the major IBD susceptibility loci. METHODS: This linkage study encompassed 904 affected relative pairs, representing the largest combined phenotyped cohort to date, and allowing for meaningful subset analyses. Genetic linkage data were stratified by disease location and age at diagnosis. RESULTS: We establish that some loci, notably the IBD3 and chromosome 3q linkage regions demonstrate contributions from both small intestine and colon cohorts, whereas others, notably the IBD1 (NOD2/CARD15) and IBD2 regions increase risk for small intestine or colon inflammation, respectively. The strongest linkage evidence in this study was for the subset of extensive ulcerative colitis in the region of IBD2 (lod 3.27; p < 0.001). Evidence for linkage in the region of NOD2/CARD15 (IBD1) was stronger for the subset of Crohn's patients with ileal disease (lod 2.56; p= 0.035) compared to the overall Crohn's group, consistent with previous findings that NOD2/CARD15 variants are associated with ileal disease. CONCLUSIONS: Analyses incorporating disease location in IBD increase the power and enhance the accuracy of genomic localization. Our data provide strong evidence that extensive ulcerative colitis represents a pathophysiologic subset of IBD. More... »

PAGES

572

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1111/j.1572-0241.2006.00451.x

DOI

http://dx.doi.org/10.1111/j.1572-0241.2006.00451.x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008610257

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16542294


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