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

Authors

Heather J. Cordell, Newcastle University
Younghun Han, Dartmouth College
George F. Mells, University of Cambridge
Y Li
Gideon M. Hirschfield, University of Birmingham
Casey S. Greene, Dartmouth College
Gang Xie, University of Toronto/Lunenfeld-Tanenbaum Research Institute
Brian D. Juran, Mayo Clinic Rochester, MN
Dakai Zhu, Dartmouth College
David C. Qian, Dartmouth College
James A.B. Floyd, Queen Mary University of London
Katherine I. Morley, King's College London
Daniele Prati, Alessandro Manzoni Hospital
Ana Lleo, IRCCS Istituto Clinico Humanitas - Rozzano (Milano)
Daniele Cusi, National Research Council of Italy
Erik M. Schlicht, Mayo Clinic Rochester, MN
Craig Lammert, Mayo Clinic Rochester, MN
Elizabeth J. Atkinson, Mayo Clinic Rochester, MN
LL Chan
Andrade M de
Tobias Balschun, Kiel University
Andrew L. Mason, University of Alberta
Robert P. Myers, University of Calgary
Jinyi Zhang, University of Toronto/Lunenfeld-Tanenbaum Research Institute
Piotr Milkiewicz, Pomeranian Medical University in Szczecin
Jia Qu, Wenzhou Medical University
Joseph A. Odin, Icahn School of Medicine at Mount Sinai
Velimir A. Luketic, Virginia Commonwealth University
Bruce R. Bacon, Saint Louis University
Henry C. Bodenheimer, Yeshiva University

Abstract

AbstractPrimary 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.

DOI

10.1038/ncomms9019

Publication Date

2015-09-22

Publication Title

Nature Communications

Volume

6

Issue

1

ISSN

2041-1723

Recommended Citation

Cordell, H., Han, Y., Mells, G., Li, Y., Hirschfield, G., Greene, C., Xie, G., Juran, B., Zhu, D., Qian, D., Floyd, J., Morley, K., Prati, D., Lleo, A., Cusi, D., Schlicht, E., Lammert, C., Atkinson, E., Chan, L., de, A., Balschun, T., Mason, A., Myers, R., Zhang, J., Milkiewicz, P., Qu, J., Odin, J., Luketic, V., Bacon, B., & Bodenheimer, H. (2015) 'International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways', Nature Communications, 6(1). Available at: 10.1038/ncomms9019