Reference : Novel Crohn disease locus identified by genome-wide association maps to a gene desert...
Scientific journals : Article
Life sciences : Veterinary medicine & animal health
Human health sciences : Gastroenterology & hepatology
http://hdl.handle.net/2268/101956
Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4.
English
Libioulle, Cécile mailto [Université de Liège - ULg > > Génétique >]
Louis, Edouard mailto [Université de Liège - ULg > Département des sciences cliniques > Hépato-gastroentérologie - Relations académiques et scientifiques (Médecine) >]
Hansoul, Sarah [Université de Liège - ULg > Département de productions animales > GIGA-R : Génomique animale >]
Sandor, Cynthia mailto [Université de Liège - ULg > Département de productions animales > Génomique animale >]
Farnir, Frédéric mailto [Université de Liège - ULg > Département de productions animales > Biostatistique, économie, sélection animale >]
Franchimont, Denis [> > > >]
Vermeire, Severine [> > > >]
Dewit, Olivier [> > > >]
de Vos, Martine [Ghent University Hospital > Department of Hepatology and Gastroenterology > > >]
Dixon, Anna [> > > >]
Demarche, Bruno [> > > >]
Gut, Ivo [> > > >]
Heath, Simon [> > > >]
Foglio, Mario [> > > >]
Liang, Liming [> > > >]
Laukens, Debby [> > > >]
Mni, Myriam [Université de Liège - ULg > Département de productions animales > GIGA-R : Génomique animale >]
Zelenika, Diana [> > > >]
Van Gossum, Andre [> > > >]
Rutgeerts, Paul [> > > >]
Belaiche, Jacques [Centre Hospitalier Universitaire de Liège - CHU > > Gastro-Entérologie-Hépatologie >]
Lathrop, Mark [> > > >]
Georges, Michel mailto [Université de Liège - ULg > Département de productions animales > Génomique animale >]
2007
PLoS Genetics
Public Library of Science
3
4
538-543
Yes (verified by ORBi)
International
1553-7390
1553-7404
San Francisco
CA
[en] Base Sequence ; Case-Control Studies ; Chromosome Mapping ; Chromosomes, Human, Pair 5 ; Cohort Studies ; Crohn Disease/genetics ; Gene Expression Regulation ; Gene Frequency ; Genetic Predisposition to Disease ; Haplotypes ; Humans ; Linkage Disequilibrium ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; Receptors, Prostaglandin E/genetics ; Sequence Homology, Nucleic Acid
[en] To identify novel susceptibility loci for Crohn disease (CD), we undertook a genome-wide association study with more than 300,000 SNPs characterized in 547 patients and 928 controls. We found three chromosome regions that provided evidence of disease association with p-values between 10(-6) and 10(-9). Two of these (IL23R on Chromosome 1 and CARD15 on Chromosome 16) correspond to genes previously reported to be associated with CD. In addition, a 250-kb region of Chromosome 5p13.1 was found to contain multiple markers with strongly suggestive evidence of disease association (including four markers with p < 10(-7)). We replicated the results for 5p13.1 by studying 1,266 additional CD patients, 559 additional controls, and 428 trios. Significant evidence of association (p < 4 x 10(-4)) was found in case/control comparisons with the replication data, while associated alleles were over-transmitted to affected offspring (p < 0.05), thus confirming that the 5p13.1 locus contributes to CD susceptibility. The CD-associated 250-kb region was saturated with 111 SNP markers. Haplotype analysis supports a complex locus architecture with multiple variants contributing to disease susceptibility. The novel 5p13.1 CD locus is contained within a 1.25-Mb gene desert. We present evidence that disease-associated alleles correlate with quantitative expression levels of the prostaglandin receptor EP4, PTGER4, the gene that resides closest to the associated region. Our results identify a major new susceptibility locus for CD, and suggest that genetic variants associated with disease risk at this locus could modulate cis-acting regulatory elements of PTGER4.
Researchers ; Professionals
http://hdl.handle.net/2268/101956
also: http://hdl.handle.net/2268/26637
10.1371/journal.pgen.0030058

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Open access
PLoS Genetics 2007 3 538-543.pdfPublisher postprint1.65 MBView/Open

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.