Dataset Information

Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci.

ABSTRACT: Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4-7.5% of individuals with inflammatory bowel disease. We performed a genome-wide association analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 × 10?¹? and P = 4.1 × 10??, respectively).

SUBMITTER: Melum E

PROVIDER: S-EPMC4354850 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci.

Melum Espen E Franke Andre A Schramm Christoph C Weismüller Tobias J TJ Gotthardt Daniel Nils DN Offner Felix A FA Juran Brian D BD Laerdahl Jon K JK Labi Verena V Björnsson Einar E Weersma Rinse K RK Henckaerts Liesbet L Teufel Andreas A Rust Christian C Ellinghaus Eva E Balschun Tobias T Boberg Kirsten Muri KM Ellinghaus David D Bergquist Annika A Sauer Peter P Ryu Euijung E Hov Johannes Roksund JR Wedemeyer Jochen J Lindkvist Björn B Wittig Michael M Porte Robert J RJ Holm Kristian K Gieger Christian C Wichmann H-Erich HE Stokkers Pieter P Ponsioen Cyriel Y CY Runz Heiko H Stiehl Adolf A Wijmenga Cisca C Sterneck Martina M Vermeire Severine S Beuers Ulrich U Villunger Andreas A Schrumpf Erik E Lazaridis Konstantinos N KN Manns Michael P MP Schreiber Stefan S Karlsen Tom H TH

Nature genetics 20101212 1

Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4-7.5% of individuals with inflammatory bowel disease. We performed a genome-wide association analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 × 10⁻¹⁶ and P = 4.1 × 10⁻⁸, respectively). ...[more]

PMID: 21151127

Similar Datasets

Project description:Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are forms of hepatic autoimmunity, and risk for both diseases has a strong genetic component. This study aimed to define the genetic architecture of PBC and PSC within the Polish population.Subjects were 443 women with PBC, 120 patients with PSC, and 934 healthy controls recruited from Gastroenterology Departments in various Polish hospitals. Allelotyping employed a pooled-DNA sample-based genome-wide association study (GWAS) approach, using Illumina Human Omni2.5-Exome BeadChips and the following novel selection criteria for risk loci: blocks of at least 10 single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium, where the distance between each adjacent SNP pair in the block was less than 30 kb, and each SNP was associated with disease at a significance level of P < 0.005. A selected index SNP from each block was validated using TaqMan SNP genotyping assays.Nineteen and twenty-one SNPs were verified as associated with PBC and PSC, respectively, by individual genotyping; 19 (10/9, PBC/PSC) SNPs reached a stringent (corrected) significance threshold and a further 21 (9/12, PBC/PSC) reached a nominal level of significance (P < 0.05 with odds ratio (OR) > 1.2 or < 0.83), providing suggestive evidence of association. The SNPs mapped to seven (1p31.3, 3q13, 6p21, 7q32.1, 11q23.3, 17q12, 19q13.33) and one (6p21) chromosome region previously associated with PBC and PSC, respectively. The SNP, rs35730843, mapping to the POLR2G gene promoter (P = 1.2 × 10-5, OR = 0.39) demonstrated the highest effect size, and was protective for PBC, whereas for PSC respective SNPs were: rs13191240 in the intron of ADGRB3 gene (P = 0.0095, OR = 0.2) and rs3822659 (P = 0.0051, OR = 0.236) along with rs9686714 (P = 0.00077, OR = 0.2), both located in the WWC1 gene.Our cost-effective GWAS approach followed by individual genotyping confirmed several previously identified associations and discovered new susceptibility loci associated with PBC and/or PSC in Polish patients. However, further functional studies are warranted to understand the roles of these newly identified variants in the development of the two disorders.

Dataset Information

Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci.

Publications

Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets