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Genetic analysis in a Dutch study sample identifies more ulcerative colitis susceptibility loci and shows their additive role in disease risk.

Authors :
Festen EA
Stokkers PC
van Diemen CC
van Bodegraven AA
Boezen HM
Crusius BJ
Hommes DW
van der Woude CJ
Balschun T
Verspaget HW
Schreiber S
de Jong DJ
Franke A
Dijkstra G
Wijmenga C
Weersma RK
Source :
The American journal of gastroenterology [Am J Gastroenterol] 2010 Feb; Vol. 105 (2), pp. 395-402. Date of Electronic Publication: 2009 Oct 27.
Publication Year :
2010

Abstract

Objectives: Genetic susceptibility is known to make a major contribution to the pathogenesis of ulcerative colitis (UC). Recently, three studies, including a genome-wide association study (GWAS), reported novel UC risk loci.<br />Methods: The top-20 single-nucleotide polymorphisms (SNPs) from the first UC-GWAS were genotyped, as part of the study's replication phase, in 561 UC cases and 728 controls from our Dutch UC study sample. We genotyped eight SNPs identified in two more studies, in these individuals, and replicated all significantly associated SNPs in an additional 894 UC cases and 1,174 controls from our Dutch UC study sample. A combined analysis for all patients (n=1,455) and controls (n=1,902) was performed. Dose-response models were constructed with the associated risk alleles.<br />Results: We found 12 SNPs tagging ten loci, including HLA-DRA, IL10, IL23R, JAK2, S100Z, ARPC2, and ECM1, to be associated with UC. We identified 10q26, flagged by the UC-GWAS but not confirmed in its replication phase, as a UC locus and found a trend toward association for GAS7. No association with disease localization or severity was found. The dose-response models show that individuals carrying 11 or more risk alleles have an odds ratio of 8.2 (confidence interval 3.0-22.8) for UC susceptibility.<br />Conclusions: We confirmed the association of multiple loci with UC in the Dutch population and found evidence for association of 10q26 and a trend suggesting association for GAS7. Genetic models show that multiple risk loci in an individual increase the risk for developing UC.

Details

Language :
English
ISSN :
1572-0241
Volume :
105
Issue :
2
Database :
MEDLINE
Journal :
The American journal of gastroenterology
Publication Type :
Academic Journal
Accession number :
19861958
Full Text :
https://doi.org/10.1038/ajg.2009.576