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 (n¼2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n¼3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombinedo5108) 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

Maurizia Brunetto
Membro del Collaboration Group
;
2015

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 (n¼2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n¼3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombinedo5108) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist.
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; PBC Consortium, Canadian-US; Almasio, Piero L.; Alvaro, Domenico; Andreone, Pietro; Andriulli, Angelo; Barlassina, Cristina; Maria Battezzati, Pier; Benedetti, Antonio; Bernuzzi, Francesca; Bianchi, Ilaria; Consiglia Bragazzi, Maria; Brunetto, MAURIZIA ROSSANA; Bruno, Savino; Casella, Giovanni; Coco, Barbara; Colli, Agostino; Colombo, Massimo; Colombo, Silvia; Cursaro, Carmela; Saveria Crocè, Lory; Crosignani, Andrea; Francesca Donato, Maria; Elia, Gianfranco; Fabris, Luca; Ferrari, Carlo; Floreani, Annarosa; Foglieni, Barbara; Fontana, Rosanna; Galli, Andrea; Lazzari, Roberta; Macaluso, Fabio; Malinverno, Federica; Marra, Fabio; Marzioni, Marco; Mattalia, Alberto; Montanari, Renzo; Morini, Lorenzo; Morisco, Filomena; S, Mousa Hani; Muratori, Luigi; Muratori, Paolo; Niro, Grazia A.; Palmieri, Vincenzo O.; Picciotto, Antonio; Podda, Mauro; Portincasa, Piero; Ronca, Vincenzo; Rosina, Floriano; Rossi, Sonia; Sogno, Ilaria; Spinzi, Giancarlo; Spreafico, Marta; Strazzabosco, Mario; Tarallo, Sonia; Tarocchi, Mirko; Tiribelli, Claudio; Toniutto, Pierluigi; & Massimo Zuin (Italian PBC Genetics Study Group), Maria Vinci; Consortium, UK-PBC; Eric Gershwin, M.; Anderson, Carl A.; Lazaridis, Konstantinos N.; Invernizzi, Pietro; Seldin, Michael F.; Sandford, Richard N.; Amos, Christopher I.; Siminovitch, Katherine A.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/844124
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