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International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

ABSTRACT: Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

SUBMITTER: Cordell HJ

PROVIDER: S-EPMC4580981 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Cordell Heather J HJ Han Younghun Y Mells George F GF Li Yafang Y Hirschfield Gideon M GM Greene Casey S CS Xie Gang G Juran Brian D BD Zhu Dakai D Qian David C DC Floyd James A B JA Morley Katherine I KI Prati Daniele D Lleo Ana A Cusi Daniele D Gershwin M Eric ME Anderson Carl A CA Lazaridis Konstantinos N KN Invernizzi Pietro P Seldin Michael F MF Sandford Richard N RN Amos Christopher I CI Siminovitch Katherine A KA

Nature communications 20150922

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JA ...[more]

PMID: 26394269

Dataset Information

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Publications

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

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