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rdf:type |
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lifeskim:mentions |
umls-concept:C0004083,
umls-concept:C0010346,
umls-concept:C0017262,
umls-concept:C0024779,
umls-concept:C0079429,
umls-concept:C0185117,
umls-concept:C0205314,
umls-concept:C0205396,
umls-concept:C0679622,
umls-concept:C1419064,
umls-concept:C1521455,
umls-concept:C1708726,
umls-concept:C2911684
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pubmed:issue |
4
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pubmed:dateCreated |
2007-5-21
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pubmed:abstractText |
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.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-10607616,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-11385576,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-11731797,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-11927615,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-12111667,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-12538238,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-12925520,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-15107849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-15107852,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-15489855,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-15838508,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-15861209,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-16024819,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-16221758,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-16354752,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-17068223,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-17200669,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17447842-6361290
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1553-7404
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pubmed:author |
pubmed-author:BelaicheJacquesJ,
pubmed-author:DemarcheBrunoB,
pubmed-author:DewitOlivierO,
pubmed-author:DixonAnnaA,
pubmed-author:FarnirFrédéricF,
pubmed-author:FoglioMarioM,
pubmed-author:FranchimontDenisD,
pubmed-author:GeorgesMichelM,
pubmed-author:HansoulSarahS,
pubmed-author:HeathSimonS,
pubmed-author:KimK-MKM,
pubmed-author:LathropMarkM,
pubmed-author:LaukensDebbyD,
pubmed-author:LiangLimingL,
pubmed-author:LibioulleCécileC,
pubmed-author:LouisEdouardE,
pubmed-author:MniMyriamM,
pubmed-author:RutgeertsPaulP,
pubmed-author:SandorCynthiaC,
pubmed-author:Van GossumAndréA,
pubmed-author:VermeireSéverineS,
pubmed-author:ZelenikaDianaD,
pubmed-author:de VosMartineM
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pubmed:issnType |
Electronic
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pubmed:day |
20
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pubmed:volume |
3
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
e58
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17447842-Base Sequence,
pubmed-meshheading:17447842-Case-Control Studies,
pubmed-meshheading:17447842-Chromosome Mapping,
pubmed-meshheading:17447842-Chromosomes, Human, Pair 5,
pubmed-meshheading:17447842-Cohort Studies,
pubmed-meshheading:17447842-Crohn Disease,
pubmed-meshheading:17447842-Gene Expression Regulation,
pubmed-meshheading:17447842-Gene Frequency,
pubmed-meshheading:17447842-Genetic Predisposition to Disease,
pubmed-meshheading:17447842-Haplotypes,
pubmed-meshheading:17447842-Humans,
pubmed-meshheading:17447842-Linkage Disequilibrium,
pubmed-meshheading:17447842-Molecular Sequence Data,
pubmed-meshheading:17447842-Polymorphism, Single Nucleotide,
pubmed-meshheading:17447842-Receptors, Prostaglandin E,
pubmed-meshheading:17447842-Receptors, Prostaglandin E, EP4 Subtype,
pubmed-meshheading:17447842-Sequence Homology, Nucleic Acid
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pubmed:year |
2007
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pubmed:articleTitle |
Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4.
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pubmed:affiliation |
Unit of Animal Genomics, GIGA-R and Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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