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

Cordell, Heather J.; Han, Younghun; Mells, George F.; Yafang, Li; 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,; Eric Gershwin, M.; Anderson, Carl A.; Lazaridis, Konstantinos N.; Invernizzi, Pietro; Seldin, Michael F.; Sandford, Richard N.; Amos, Christopher I.; Siminovitch, Katherine A.; Tiribelli, Claudio

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 (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways / Heather J., C., Younghun, H., George F., M., Yafang, L.i., Gideon M., H., Casey S., G., Gang, X., Brian D., J., Dakai, Z., David C., Q., James A. B., F., Katherine I., M., Daniele, P., Ana, L., Daniele, C., Canadian US PBC, C., Italian PBC Genetics Study, G., UK PBC, C., M., E.G., Carl A., A., et al.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - ELETTRONICO. - 6(2015):Sept(2015), pp. 8019.1-8019.11. [10.1038/ncomms9019]