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, Cambridge University
Yafang Li, Dartmouth College
Gideon M. Hirschfield, University of Birmingham
Casey S. Greene, Dartmouth CollegeFollow
Gang Xie, Mount Sinai Hospital, Lunenfeld-Tanenbaum Research Institute and Toronto General Research Institute
Brian D. Juran, Mayo Clinic, Rochester, Minnesota
Dakai Zhu, Dartmouth College
David C. Qian, Dartmouth College
James A.B Floyd, Queen Mary University of London
Katherine I. Morley, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus
Daniele Prati, Ospedale Alessandro Manzoni
Ana Lleo, Universita degli Studi di Milano
Daniele Cusi, Universita degli Studi di Milano
Canadian–US PBC Consortium
Italian PBC Genetics Study Group
UK-PBC Consortium
M. Eric Gershwin, University of California, Davis
Carl A. Anderson, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton
Konstantinos N. Lazaridis, Mayo Clinic, Rochester, Minnesota
Pietro Invernizzi, University of California, Davis
Michael F. Seldin, University of California, Davis
Richard N. Sandford, Cambridge University
Christopher I. Amos, Dartmouth CollegeFollow
Katherine A. Siminovitch, University of Toronto

Document Type

Article

Publication Date

9-22-2015

Publication Title

Nature Communications

Department

Geisel School of Medicine

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 (P_combined<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

Dartmouth Digital Commons Citation

Cordell, Heather J.; Han, Younghun; Mells, George F.; Li, Yafang; Hirschfield, Gideon M.; Greene, Casey S.; Xie, Gang; Juran, Brian D.; Zhu, Dakai; Qian, David C.; Floyd, James A.B; Morley, Katherine I.; Prati, Daniele; Lleo, Ana; Cusi, Daniele; Canadian–US PBC Consortium; Italian PBC Genetics Study Group; UK-PBC Consortium; Gershwin, M. Eric; Anderson, Carl A.; Lazaridis, Konstantinos N.; Invernizzi, Pietro; Seldin, Michael F.; Sandford, Richard N.; Amos, Christopher I.; and Siminovitch, Katherine A., "International Genome-Wide Meta-Analysis Identifies New Primary Biliary Cirrhosis Risk Loci and Targetable Pathogenic Pathways" (2015). Dartmouth Scholarship. 2874.
https://digitalcommons.dartmouth.edu/facoa/2874