title: Genome-wide association study for Crohn's disease in the Quebec Founder Population identifies multiple validated disease loci.
abstract: 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 loci NOD2 and IBD5. The recently described IL23R locus 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 near JAKMIP1 on 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.
authors.affiliation: Genizon BioSciences, Inc., St. Laurent, QC, Canada H4T 2C7. john.raelson@genizon.com
authors.forename: John V
authors.initials: JV
authors.lastname: Raelson
authors.forename: Randall D
authors.initials: RD
authors.lastname: Little
authors.forename: Andreas
authors.initials: A
authors.lastname: Ruether
authors.forename: Hélène
authors.initials: H
authors.lastname: Fournier
authors.forename: Bruno
authors.initials: B
authors.lastname: Paquin
authors.forename: Paul
authors.initials: P
authors.lastname: Van Eerdewegh
authors.forename: W E C
authors.initials: WE
authors.lastname: Bradley
authors.forename: Pascal
authors.initials: P
authors.lastname: Croteau
authors.forename: Quynh
authors.initials: Q
authors.lastname: Nguyen-Huu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Segal
authors.forename: Sophie
authors.initials: S
authors.lastname: Debrus
authors.forename: René
authors.initials: R
authors.lastname: Allard
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Gunnar
authors.initials: G
authors.lastname: Jacobs
authors.forename: Susanna
authors.initials: S
authors.lastname: Nikolaus
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vidal
authors.forename: Peter
authors.initials: P
authors.lastname: Szego
authors.forename: Nathalie
authors.initials: N
authors.lastname: Laplante
authors.forename: Hilary F
authors.initials: HF
authors.lastname: Clark
authors.forename: René J
authors.initials: RJ
authors.lastname: Paulussen
authors.forename: John W
authors.initials: JW
authors.lastname: Hooper
authors.forename: Tim P
authors.initials: TP
authors.lastname: Keith
authors.forename: Abdelmajid
authors.initials: A
authors.lastname: Belouchi
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
mesh_terms: D000483:Alleles; D002886:Chromosomes, Human, Pair 17; D002893:Chromosomes, Human, Pair 3; D002894:Chromosomes, Human, Pair 4; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology; D018703:Founder Effect; D005602:France / Q000208:ethnology; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D020161:Physical Chromosome Mapping; D011792:Quebec; D018123:Receptors, Interleukin / Q000235:genetics; D015203:Reproducibility of Results; D012307:Risk Factors