A meta-analysis of genome-wide association scans identifies IL18RAP, PTPN2, TAGAP, and PUS10 as shared risk loci for Crohn's disease and celiac disease.
PLoS Genet
; 7(1): e1001283, 2011 Jan 27.
Article
em En
| MEDLINE
| ID: mdl-21298027
ABSTRACT
Crohn's disease (CD) and celiac disease (CelD) are chronic intestinal inflammatory diseases, involving genetic and environmental factors in their pathogenesis. The two diseases can co-occur within families, and studies suggest that CelD patients have a higher risk to develop CD than the general population. These observations suggest that CD and CelD may share common genetic risk loci. Two such shared loci, IL18RAP and PTPN2, have already been identified independently in these two diseases. The aim of our study was to explicitly identify shared risk loci for these diseases by combining results from genome-wide association study (GWAS) datasets of CD and CelD. Specifically, GWAS results from CelD (768 cases, 1,422 controls) and CD (3,230 cases, 4,829 controls) were combined in a meta-analysis. Nine independent regions had nominal association p-value <1.0 x 10â»5 in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value < 1 x 10⻲ in CelD and < 1 x 10⻳ in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37 x 10â»8 and 6.39 x 10â»9, respectively, in the meta-analysis. The other seven had not been reported as shared loci and thus were tested in additional CelD (3,149 cases and 4,714 controls) and CD (1,835 cases and 1,669 controls) cohorts. Two of these loci, TAGAP and PUS10, showed significant evidence of replication (Bonferroni corrected p-values <0.0071) in the combined CelD and CD replication cohorts and were firmly established as shared risk loci of genome-wide significance, with overall combined p-values of 1.55 x 10⻹° and 1.38 x 10⻹¹ respectively. Through a meta-analysis of GWAS data from CD and CelD, we have identified four shared risk loci PTPN2, IL18RAP, TAGAP, and PUS10. The combined analysis of the two datasets provided the power, lacking in the individual GWAS for single diseases, to detect shared loci with a relatively small effect.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Crohn
/
Doença Celíaca
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Predisposição Genética para Doença
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Proteínas Ativadoras de GTPase
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Subunidade beta de Receptor de Interleucina-18
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Proteína Tirosina Fosfatase não Receptora Tipo 2
/
Hidroliases
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
PLoS Genet
Ano de publicação:
2011
Tipo de documento:
Article