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Annese, V

Barisani, D

Beauchamp, C

Boucher, G

Daly, MJ

Dubois, PC

Festen, EAM

Goyette, P

Green, T

Hommes, DW

Lagace, C

Palmieri, O

Rioux, JD

Stokkers, PCF

Trynka, G

van Heel, DA

Weersma, RK

Wijmenga, C

PLoS Genetics

English

PubMed

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 &lt;1.0 x 10⁻⁵ in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value &lt; 1 x 10⁻² in CelD and &lt; 1 x 10⁻³ in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37 x 10⁻⁸ and 6.39 x 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 &lt;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 10⁻¹⁰ and 1.38 x 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

Festen, Eleonora AM

Goyette, Philippe

Green, Todd

Boucher, Gabrielle

Beauchamp, Claudine

Trynka, Gosia

Dubois, Patrick C

Lagacé, Caroline

Stokkers, Pieter CF

Hommes, Daan W

Barisani, Donatella

Palmieri, Orazio

Annese, Vito

van Heel, David A

Weersma, Rinse K

Daly, Mark J

Wijmenga, Cisca

Rioux, John D

eScholarship - University of California

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

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 10⁻⁵ in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value < 1 x 10⁻² in CelD and < 1 x 10⁻³ in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37 x 10⁻⁸ and 6.39 x 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 <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 10⁻¹⁰ and 1.38 x 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

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

Directory of Open Access Journals

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.

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 <1.0x10(-5) in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value <1x10(-2) in CelD and <1x10(-3) in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37x10(-8) and 6.39x10(-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 1.55x10(-10) and 1.38x10(-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.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Festen, E.A.M.

Goyette, P.

Green, T.

Boucher, G.

Beauchamp, C.

Trynka, G.

Dubois, P.C.

Lagace, C.

Stokkers, P.C.F.

Hommes, D.W.

Barisani, D.

Palmieri, O.

Annese, V.

Heel, D.A. van

Weersma, R.K.

Daly, M.J.

Wijmenga, C.

Rioux, J.D.

Leiden University Scholary Publications

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 &lt;1.0x10(-5) in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value &lt;1x10(-2) in CelD and &lt;1x10(-3) in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37x10(-8) and 6.39x10(-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, &lt;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 1.55x10(-10) and 1.38x10(-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 effec

van Heel, D.A.

UvA-DARE

Queen Mary Research Online

A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21.

A new multipoint method for genome-wide association studies by imputation of genotypes.

A unified approach to genotype imputation and haplotype-phase inference for large data sets of trios and unrelated individuals.

Abecasis GR (2006) MACH 1.0: Rapid haplotype reconstruction and missing genotype inference.

Carding SR

Genetic analysis in a Dutch study sample identifies more ulcerative colitis susceptibility loci and shows their additive role in disease risk.

Genetic analysis of innate immunity in Crohn’s disease and ulcerative colitis identifies two susceptibility loci harboring CARD9 and IL18RAP.

Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis.

Genomewide association defines more than 30 distinct susceptibility loci for Crohn’s disease.

Genomewide association identifies multiple ulcerative colitis susceptibility loci.

Haplotype-based association analysis of 56 functional candidate genes in the IBD6 locus on chromosome 19.

High prevalence of celiac disease among patients affected by Crohn’s disease.

Induction of RhoGAP and pathological changes characteristic of Alzheimer’s disease by UAHFEMF discharge in rat brain.

Inflammatory bowel disease and celiac disease: overlaps in the pathology and genetics, and their potential drug targets. Endocr Metab Immune Disord Drug Targets 9:

Inflammatory bowel disease: clinical aspects and established and evolving therapies.

Meta-analysis of genome-wide association studies with overlapping subjects.

Molecular prediction of disease risk and severity in a large Dutch Crohn’s disease cohort.

Multiple common variants for celiac disease influencing immune gene expression.

Newly identified genetic risk variants for celiac disease related to the immune response.

Philippe Goyette3., Todd Green4., Gabrielle Boucher3, Claudine Beauchamp3, Gosia Trynka2, Patrick

PLINK: a tool set for whole-genome association and population-based linkage analyses.

Recent advances in coeliac disease genetics.

Recent advances in coeliac disease.

Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility.

Shared and distinct genetic variants in type 1 diabetes and celiac disease.

The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases.

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 <1.0x10(-5) in this meta-analysis and showed evidence of association to the individual diseases in the original scans (p-value <1x10(-2) in CelD and <1x10(-3) in CD). These include the two previously reported shared loci, IL18RAP and PTPN2, with p-values of 3.37x10(-8) and 6.39x10(-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 1.55x10(-10) and 1.38x10(-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 effec

NARCIS 

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</p

Festen, Eleonora A. M.

Dubois, Patrick C.

Lagace, Caroline

Stokkers, Pieter C. F.

Hommes, Daan W.

van Heel, David A.

Weersma, Rinse K.

Daly, Mark J.

Rioux, John D.

ARTS repository - University of Groningen

University of Groningen

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-valu

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

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Directory of Open Access Journals

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Queen Mary Research Online

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ARTS repository - University of Groningen

University of Groningen

NARCIS