Genetic Susceptibility in IBD: Overlap Between Ulcerative Colitis and Crohn's Disease

James Doecke, Lisa Simms, Zhen Zhen Zhao, Ning Huang, Katherine Hanigan, Krupa Krishnaprasad, Rebecca Roberts, Jane Andrews, Gillian Mahy, Peter Bampton, Peter Lewindon, Timothy Florin, Ian Lawrance, Richard Gearry, Grant Montgomery, Graham Radford-Smith

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    25 Citations (Scopus)

    Abstract

    Background: The etiology of ulcerative colitis (UC) and Crohn's disease (CD) involves both genetic and environmental components. Multiple UC and CD susceptibility genes have been identified through genome-wide association studies and subsequent meta-analyses. These studies have also highlighted the presence of genes common to both diseases, and shared with several other autoimmune disorders. The aim of this study was to identify single nucleotide polymorphisms (SNPs) recently identified by the International IBD Genetics Consortium (IIBDGC) demonstrating that highly significant associations with CD could also confer genetic susceptibility to UC. Methods: Statistical modeling was performed on 29 CD-associated SNPs. The study comprised of 1652 UC cases from the Australia and New Zealand IBD Consortium and 2363 Australian population-based controls. Results: After adjustment for multiple comparisons, only one SNP, rs3024505, was significantly associated with UC (P 1/4 0.001). Independent chisquare analyses identified odds ratios of 2.22 (1.48-3.37) for the rare homozygous genotype, and 1.20 (1.06-1.35) for the minor allele. Five other SNPs demonstrated moderate to weak associations with UC. Conclusions: Of the 29 SNPs conferring high genetic susceptibility to CD, 28 were not associated with UC, thus indicating that for this SNP set there is a low level of overlap between the two major forms of IBD. Only one SNP, rs3024505 (Chr 1q32.1, upstream of IL10), was associated with susceptibility to UC. The identification of this SNP replicates a finding from Franke et al (2008), where the rs3024505 SNP was strongly associated with UC across multiple European populations.

    Original languageEnglish
    Pages (from-to)240-245
    Number of pages6
    JournalInflammatory Bowel Diseases
    Volume19
    Issue number2
    DOIs
    Publication statusPublished - 2013

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  • Cite this

    Doecke, J., Simms, L., Zhao, Z. Z., Huang, N., Hanigan, K., Krishnaprasad, K., Roberts, R., Andrews, J., Mahy, G., Bampton, P., Lewindon, P., Florin, T., Lawrance, I., Gearry, R., Montgomery, G., & Radford-Smith, G. (2013). Genetic Susceptibility in IBD: Overlap Between Ulcerative Colitis and Crohn's Disease. Inflammatory Bowel Diseases, 19(2), 240-245. https://doi.org/10.1097/MIB.0b013e3182810041