Dataset Information

Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.

ABSTRACT: Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1 x 10(-13), combined odds ratio OR = 0.73) and 12q15 (rs1558744, combined P = 2.5 x 10(-12), combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0 x 10(-16), combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3 x 10(-8), combined OR = 0.56; rs10889677, combined P = 1.3 x 10(-8), combined OR = 1.29).

SUBMITTER: Silverberg MS

PROVIDER: S-EPMC2652837 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.

Silverberg Mark S MS Cho Judy H JH Rioux John D JD McGovern Dermot P B DP Wu Jing J Annese Vito V Achkar Jean-Paul JP Goyette Philippe P Scott Regan R Xu Wei W Barmada M Michael MM Klei Lambertus L Daly Mark J MJ Abraham Clara C Bayless Theodore M TM Bossa Fabrizio F Griffiths Anne M AM Ippoliti Andrew F AF Lahaie Raymond G RG Latiano Anna A Paré Pierre P Proctor Deborah D DD Regueiro Miguel D MD Steinhart A Hillary AH Targan Stephan R SR Schumm L Philip LP Kistner Emily O EO Lee Annette T AT Gregersen Peter K PK Rotter Jerome I JI Brant Steven R SR Taylor Kent D KD Roeder Kathryn K Duerr Richard H RH

Nature genetics 20090104 2

Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and preexisting data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identifie ...[more]

PMID: 19122664

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Project description:Ulcerative colitis (UC), a complex polygenic disorder, is one of the main subphenotypes of inflammatory bowel disease. A comprehensive dissection of the genetic etiology of UC needs to assess the contribution of rare genetic variants including copy number variations (CNVs) to disease risk. In this study, we performed a multi-step genome-wide case-control analysis to interrogate the presence of disease-relevant rare copy number variants.One thousand one hundred twenty-one German UC patients and 1770 healthy controls were initially screened for rare deletions and duplications employing SNP-array data. Quantitative PCR and high density custom array-CGH were used for validation of identified CNVs and fine mapping. Two main follow-up panels consisted of an independent cohort of 451 cases and 1274 controls, in which CNVs were assayed through quantitative PCR, and a British cohort of 2396 cases versus 4886 controls with CNV genotypes based on array data. Additional sample sets were assessed for targeted and in silico replication.Twenty-four rare copy number variants (14 deletions and 10 duplications), overrepresented in UC patients were identified in the initial screening panel. Follow-up of these CNV regions in four independent case-control series as well as an additional public in silico control group (totaling 4439 UC patients and 15,961 healthy controls) revealed three copy number variants enriched in UC patients; a 15.8 kb deletion upstream of ABCC4 and CLDN10 at13q32.1 (0.43% cases, 0.11% controls), a 119 kb duplication at 7p22.1, overlapping RNF216, ZNF815, OCM and CCZ1 (0.13% cases, 0.01% controls) and a 134 kb large duplication upstream of the KCNK9 gene at 8q24.3 (0.22% carriers among cases, 0.03% carriers among controls). The trend of association with UC was present after the P-values were corrected for combining data from different subpopulations. Break-point mapping of the deleted region suggested non-allelic homologous recombination as the mechanism underlying its formation.Our study presents a pragmatic approach for effective rare CNV screening of SNP-array data sets and implicates the potential contribution of rare structural variants in the pathogenesis of UC.

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Dataset Information

Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.

Publications

Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.

Similar Datasets

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