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Meta-Analysis
. 2015 Sep 22:6:8019.
doi: 10.1038/ncomms9019.

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

Heather J Cordell  1 , Younghun Han  2 , George F Mells  3 , Yafang Li  2 , Gideon M Hirschfield  4 , Casey S Greene  5 , Gang Xie  6 , Brian D Juran  7 , Dakai Zhu  2 , David C Qian  2 , James A B Floyd  8   9 , Katherine I Morley  8   10 , Daniele Prati  11 , Ana Lleo  12 , Daniele Cusi  13   14 ; Canadian-US PBC Consortium; Italian PBC Genetics Study Group; UK-PBC Consortium; M Eric Gershwin  15 , Carl A Anderson  8 , Konstantinos N Lazaridis  7 , Pietro Invernizzi  12   15 , Michael F Seldin  15 , Richard N Sandford  3 , Christopher I Amos  2 , Katherine A Siminovitch  6   16   17   18
Collaborators, Affiliations
Meta-Analysis

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

Heather J Cordell et al. Nat Commun. .

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.

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