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

Heather J Cordell, Younghun Han, George F Mells, Yafang Li, Gideon M Hirschfield, Casey S Greene, Gang Xie, Brian D Juran, Dakai Zhu, David C Qian, James A B Floyd, Katherine I Morley, Daniele Prati, Ana Lleo, Daniele Cusi, M Eric Gershwin, Carl A Anderson, Konstantinos N Lazaridis, Pietro Invernizzi, Michael F SeldinRichard N Sandford, Christopher I Amos, Katherine A Siminovitch, Canadian-US PBC Consortium

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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.

Original languageEnglish
Article number8019
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 22 Sept 2015

Keywords

  • genome-wide
  • meta-analysis

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