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; Gershwin, M. Eric; Anderson, Carl A.; Lazaridis, Konstantinos N.; Invernizzi, Pietro; Seldin, Michael F.; Sandford, Richard N.; Amos, Christopher I.; Siminovitch, Katherine A.; Schlicht, Erik M.; Lammert, Craig; Atkinson, Elizabeth J.; Chan, Landon L.; De Andrade, Mariza; Balschun, Tobias; Mason, Andrew L.; Myers, Robert P.; Zhang, Jinyi; Milkiewicz, Piotr; Jia, Qu; Odin, Joseph A.; Luketic, Velimir A.; Bacon, Bruce R.; Bodenheimer, Henry C.; Liakina, Valentina; Vincent, Catherine; Levy, Cynthia; Gregersen, Peter K.; Almasio, Piero L.; Alvaro, Domenico

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 ¼ 2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n ¼ 3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombinedo5 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 / Cordell, H.J., Han, Y., Mells, G.F., Li, Y., Hirschfield, G.M., Greene, C.S., Xie, G., Juran, B.D., Zhu, D., Qian, D.C., Floyd, J.A.B., Morley, K.I., Prati, D., Lleo, A., Cusi, D., Canadian US, P.C., Italian, P.G.S.G., UK PBC, C., Gershwin, M.E., Anderson, C.A., et al.. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 6:(2015), pp. 1-11. [10.1038/ncomms9019]