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

• Published in: Nature communications Vol. 6; no. 1; p. 8019
• Main Authors: 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, Gershwin, M. Eric, Anderson, Carl A., Lazaridis, Konstantinos N., Invernizzi, Pietro, Seldin, Michael F., Sandford, Richard N., Amos, Christopher I., Siminovitch, Katherine A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.09.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 38/43; 631/80/86; 692/420/2489/144; 692/699/1503/1607/1606; 692/700/139/422; Consortia; Datasets; Genetics; Genome-Wide Association Study; Genomes; Humanities and Social Sciences; Humans; Liver cirrhosis; Liver Cirrhosis, Biliary - genetics; Liver diseases; Medicine; Meta-analysis; multidisciplinary; Regression analysis; Research centers; Science; Science (multidisciplinary); Canada; United Kingdom > UK; United States > US; New Hampshire; Italy; California; Toronto Ontario Canada
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms9019

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. Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al . a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.