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

Research output: Contribution to journalArticlepeer-review


  • Heather J Cordell
  • Younghun Han
  • George F Mells
  • Yafang Li
  • Gideon 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 Seldin
  • Richard N Sandford
  • Christopher I Amos
  • Katherine A Siminovitch
  • Canadian-US PBC Consortium

Colleges, School and Institutes


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
Publication statusPublished - 22 Sep 2015


  • genome-wide, meta-analysis