Genome-wide association study for Crohn's disease in the Quebec Founder Population identifies multiple validated disease loci
| Autor: | Peter L Szego, Helene Fournier, Jean-Michel Vidal, Bruno Paquin, Susanna Nikolaus, Walter Edward Bradley, Sophie Debrus, Hilary Clark, Paul Van Eerdewegh, Stefan Schreiber, René J. A. Paulussen, René Allard, Quynh Nguyen-Huu, Nathalie Laplante, Gunnar Jacobs, Pascal Croteau, Philip Rosenstiel, Tim Keith, Andre Franke, Randall D. Little, Jonathan Segal, Andreas Ruether, John W. Hooper, Abdelmajid Belouchi, John Verner Raelson |
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| Rok vydání: | 2007 |
| Předmět: |
Genetic Markers
Candidate gene Nod2 Signaling Adaptor Protein Locus (genetics) Genome-wide association study Biology Crohn Disease Risk Factors Humans Genetic Predisposition to Disease Allele Gene Alleles Genetics Multidisciplinary Genome Human Haplotype Quebec Reproducibility of Results Receptors Interleukin Biological Sciences Physical Chromosome Mapping Founder Effect Chromosome 17 (human) Genetics Population Haplotypes Chromosomes Human Pair 3 France Chromosomes Human Pair 4 Founder effect Chromosomes Human Pair 17 |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 104(37) |
| ISSN: | 0027-8424 |
| Popis: | Genome-wide association (GWA) studies offer a powerful unbiased method for the identification of multiple susceptibility genes for complex diseases. Here we report the results of a GWA study for Crohn's disease (CD) using family trios from the Quebec Founder Population (QFP). Haplotype-based association analyses identified multiple regions associated with the disease that met the criteria for genome-wide significance, with many containing a gene whose function appears relevant to CD. A proportion of these were replicated in two independent German Caucasian samples, including the established CD lociNOD2andIBD5. The recently describedIL23Rlocus was also identified and replicated. For this region, multiple individuals with all major haplotypes in the QFP were sequenced and extensive fine mapping performed to identify risk and protective alleles. Several additional loci, including a region on 3p21 containing several plausible candidate genes, a region nearJAKMIP1on 4p16.1, and two larger regions on chromosome 17 were replicated. Together with previously published loci, the spectrum of CD genes identified to date involves biochemical networks that affect epithelial defense mechanisms, innate and adaptive immune response, and the repair or remodeling of tissue. |
| Databáze: | OpenAIRE |
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