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

Eleonora A M Festen, Philippe Goyette, Todd Green, Gabrielle Boucher, Claudine Beauchamp, Gosia Trynka, Patrick C. Dubois, Caroline Lagacé, Pieter C F Stokkers, Daan W. Hommes, Donatella Barisani, Orazio Palmieri, Vito Annese, David A. van Heel, Rinse K. Weersma, Mark J. Daly, Cisca Wijmenga, John D. Rioux

Research output: Contribution to journalArticlepeer-review

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 -5 in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value -2 in CelD and -3in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37×10-8 and 6.39×10-9, 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 -10 and 1.38×10-11 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.

Original languageEnglish
Article numbere1001283
JournalPLoS Genetics
Volume7
Issue number1
DOIs
Publication statusPublished - 2011

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this