Article (Scientific journals)
Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4.
Libioulle, Cécile; Louis, Edouard; Hansoul, Sarah et al.
2007In PLoS Genetics, 3 (4), p. 538-543
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Keywords :
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
Abstract :
[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.
Disciplines :
Veterinary medicine & animal health
Gastroenterology & hepatology
Author, co-author :
Libioulle, Cécile  ;  Université de Liège - ULiège > Génétique
Louis, Edouard  ;  Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie - Relations académiques et scientifiques (Médecine)
Hansoul, Sarah ;  Université de Liège - ULiège > Département de productions animales > GIGA-R : Génomique animale
Sandor, Cynthia ;  Université de Liège - ULiège > Département de productions animales > Génomique animale
Farnir, Frédéric  ;  Université de Liège - ULiège > 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 - ULiège > 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  ;  Université de Liège - ULiège > Département de productions animales > Génomique animale
More authors (13 more) Less
Language :
English
Title :
Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4.
Publication date :
2007
Journal title :
PLoS Genetics
ISSN :
1553-7390
eISSN :
1553-7404
Publisher :
Public Library of Science, San Francisco, United States - California
Volume :
3
Issue :
4
Pages :
538-543
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 26 October 2009

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