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

Heather J. Cordell; Younghun Han; George F. Mells; Y Li; Gideon M. Hirschfield; Casey S. Greene; Gang Xie; Brian D. Juran; Dakai Zhu; David C. Qian; James A.B. Floyd; Katherine I. Morley; Daniele Prati; Ana Lleo; Daniele Cusi; Erik M. Schlicht; Craig Lammert; Elizabeth J. Atkinson; LL Chan; Andrade M de; Tobias Balschun; Andrew L. Mason; Robert P. Myers; Jinyi Zhang; Piotr Milkiewicz; Jia Qu; Joseph A. Odin; Velimir A. Luketic; Bruce R. Bacon; Henry C. Bodenheimer; Valentina Liakina; Catherine Vincent; Cynthia Levy; Peter K. Gregersen; Piero L. Almasio; Domenico Alvaro; Pietro Andreone; Angelo Andriulli; Cristina Barlassina; Pier Maria Battezzati; Antonio Benedetti; Francesca Bernuzzi; Ilaria Bianchi; Maria Consiglia Bragazzi; Maurizia Brunetto; Savino Bruno; Giovanni Casella; Barbara Coco; Agostino Colli; M Colombo; S Colombo; Carmela Cursaro; Lory Saveria Crocè; Andrea Crosignani; Maria Francesca Donato; Gianfranco Elia; Luca Fabris; Carlo Ferrari; Annarosa Floreani; Barbara Foglieni; Rosanna Fontana; Andrea Galli; Roberta Lazzari; Fabio Macaluso; Federica Malinverno; Fabio Marra; Marco Marzioni; Alberto Mattalia; Renzo Montanari; Lorenzo Morini; Filomena Morisco; S M Hani; L Muratori; P Muratori; Grazia A. Niro; Vincenzo O. Palmieri; Antonio Picciotto; Mauro Podda; Piero Portincasa; Vincenzo Ronca; Floriano Rosina; Sonia Rossi; Ilaria Sogno; Giancarlo Spinzi; Marta Spreafico; Mario Strazzabosco; Sonia Tarallo; Mirko Tarocchi; Claudio Tiribelli; Pierluigi Toniutto; Maria Vinci; Matthew Cramp

doi:10.1038/ncomms9019

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

Heather J. Cordell^*
, Younghun Han
, George F. Mells
, Y Li
, Gideon M. Hirschfield
, Casey S. Greene
, Gang Xie
, Brian D. Juran
, Dakai Zhu
, David C. Qian
, James A.B. Floyd
, Katherine I. Morley
, Daniele Prati
, Ana Lleo
, Daniele Cusi
, Erik M. Schlicht
, Craig Lammert
, Elizabeth J. Atkinson
, LL Chan
, Andrade M de

Tobias Balschun, Andrew L. Mason, Robert P. Myers, Jinyi Zhang, Piotr Milkiewicz, Jia Qu, Joseph A. Odin, Velimir A. Luketic, Bruce R. Bacon, Henry C. Bodenheimer, Valentina Liakina, Catherine Vincent, Cynthia Levy, Peter K. Gregersen, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Cristina Barlassina, Pier Maria Battezzati, Antonio Benedetti, Francesca Bernuzzi, Ilaria Bianchi, Maria Consiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Giovanni Casella, Barbara Coco, Agostino Colli, M Colombo, S Colombo, Carmela Cursaro, Lory Saveria Crocè, Andrea Crosignani, Maria Francesca Donato, Gianfranco Elia, Luca Fabris, Carlo Ferrari, Annarosa Floreani, Barbara Foglieni, Rosanna Fontana, Andrea Galli, Roberta Lazzari, Fabio Macaluso, Federica Malinverno, Fabio Marra, Marco Marzioni, Alberto Mattalia, Renzo Montanari, Lorenzo Morini, Filomena Morisco, S M Hani, L Muratori, P Muratori, Grazia A. Niro, Vincenzo O. Palmieri, Antonio Picciotto, Mauro Podda, Piero Portincasa, Vincenzo Ronca, Floriano Rosina, Sonia Rossi, Ilaria Sogno, Giancarlo Spinzi, Marta Spreafico, Mario Strazzabosco, Sonia Tarallo, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Maria Vinci, Matthew Cramp

^*Corresponding author for this work

Peninsula Medical School

Newcastle University
Dartmouth College
University of Cambridge
University of Birmingham
University of Toronto/Lunenfeld-Tanenbaum Research Institute
Mayo Clinic Rochester, MN
Queen Mary University of London
Wellcome Sanger Institute
King's College London
Alessandro Manzoni Hospital
IRCCS Istituto Clinico Humanitas - Rozzano (Milano)
National Research Council of Italy
University of Milan
Kiel University
University of Alberta
University of Calgary
Pomeranian Medical University in Szczecin
Wenzhou Medical University
Icahn School of Medicine at Mount Sinai
Virginia Commonwealth University
Saint Louis University
Yeshiva University
Vilnius University
University of Montreal
University of Miami
Northwell Health System
University of Palermo
Eleonora Lorillard Spencer-Cenci Foundation
University of Bologna
IRCCS Ospedale Casa Sollievo della Sofferenza - San Giovanni Rotondo (FG)
Marche Polytechnic University
University of Rome La Sapienza
University of Pisa
Azienda Ospedaliera di Desio e Vimercate
Department of Internal Medicine, AO Provincia di Lecco
University of Trieste
IRCCS Fondazione Ca'Granda – Ospedale Maggiore Policlinico - Milano
University of Parma
University of Padua
University of Florence
Santa Croce Carle Hospital
IRCCS Ospedale Sacro Cuore Don Calabria
Magenta Hospital
University of Naples Federico II
University of Bari
University of Genoa
Gradenigo Hospital
Ospedale Valduce
University of Milan - Bicocca
Yale University
University of Udine
Niguarda Hospital

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Abstract

AbstractPrimary 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.

Original language	English
Number of pages	0
Journal	Nature Communications
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/ncomms9019
Publication status	E-pub ahead of print - 22 Sept 2015

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10.1038/ncomms9019

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

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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., Schlicht, E. M., Lammert, C., Atkinson, E. J., Chan, LL., ... Cramp, M. (2015). International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways. Nature Communications, 6(1). Advance online publication. https://doi.org/10.1038/ncomms9019

@article{91438562a26f42689496e7abcd292b68,

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

abstract = "AbstractPrimary 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.",

author = "Cordell, \{Heather J.\} and Younghun Han and Mells, \{George F.\} and Y Li and Hirschfield, \{Gideon M.\} and Greene, \{Casey S.\} and Gang Xie and Juran, \{Brian D.\} and Dakai Zhu and Qian, \{David C.\} and Floyd, \{James A.B.\} and Morley, \{Katherine I.\} and Daniele Prati and Ana Lleo and Daniele Cusi and Schlicht, \{Erik M.\} and Craig Lammert and Atkinson, \{Elizabeth J.\} and LL Chan and de, \{Andrade M\} and Tobias Balschun and Mason, \{Andrew L.\} and Myers, \{Robert P.\} and Jinyi Zhang and Piotr Milkiewicz and Jia Qu and Odin, \{Joseph A.\} and Luketic, \{Velimir A.\} and Bacon, \{Bruce R.\} and Bodenheimer, \{Henry C.\} and Valentina Liakina and Catherine Vincent and Cynthia Levy and Gregersen, \{Peter K.\} and Almasio, \{Piero L.\} and Domenico Alvaro and Pietro Andreone and Angelo Andriulli and Cristina Barlassina and Battezzati, \{Pier Maria\} and Antonio Benedetti and Francesca Bernuzzi and Ilaria Bianchi and Bragazzi, \{Maria Consiglia\} and Maurizia Brunetto and Savino Bruno and Giovanni Casella and Barbara Coco and Agostino Colli and M Colombo and S Colombo and Carmela Cursaro and Croc{\`e}, \{Lory Saveria\} and Andrea Crosignani and Donato, \{Maria Francesca\} and Gianfranco Elia and Luca Fabris and Carlo Ferrari and Annarosa Floreani and Barbara Foglieni and Rosanna Fontana and Andrea Galli and Roberta Lazzari and Fabio Macaluso and Federica Malinverno and Fabio Marra and Marco Marzioni and Alberto Mattalia and Renzo Montanari and Lorenzo Morini and Filomena Morisco and Hani, \{S M\} and L Muratori and P Muratori and Niro, \{Grazia A.\} and Palmieri, \{Vincenzo O.\} and Antonio Picciotto and Mauro Podda and Piero Portincasa and Vincenzo Ronca and Floriano Rosina and Sonia Rossi and Ilaria Sogno and Giancarlo Spinzi and Marta Spreafico and Mario Strazzabosco and Sonia Tarallo and Mirko Tarocchi and Claudio Tiribelli and Pierluigi Toniutto and Maria Vinci and Matthew Cramp",

year = "2015",

month = sep,

day = "22",

doi = "10.1038/ncomms9019",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Cordell, HJ, Han, Y, Mells, GF, Li, Y, Hirschfield, GM, Greene, CS, Xie, G, Juran, BD, Zhu, D, Qian, DC, Floyd, JAB, Morley, KI, Prati, D, Lleo, A, Cusi, D, Schlicht, EM, Lammert, C, Atkinson, EJ, Chan, LL, de, AM, Balschun, T, Mason, AL, Myers, RP, Zhang, J, Milkiewicz, P, Qu, J, Odin, JA, Luketic, VA, Bacon, BR, Bodenheimer, HC, Liakina, V, Vincent, C, Levy, C, Gregersen, PK, Almasio, PL, Alvaro, D, Andreone, P, Andriulli, A, Barlassina, C, Battezzati, PM, Benedetti, A, Bernuzzi, F, Bianchi, I, Bragazzi, MC, Brunetto, M, Bruno, S, Casella, G, Coco, B, Colli, A, Colombo, M, Colombo, S, Cursaro, C, Crocè, LS, Crosignani, A, Donato, MF, Elia, G, Fabris, L, Ferrari, C, Floreani, A, Foglieni, B, Fontana, R, Galli, A, Lazzari, R, Macaluso, F, Malinverno, F, Marra, F, Marzioni, M, Mattalia, A, Montanari, R, Morini, L, Morisco, F, Hani, SM, Muratori, L, Muratori, P, Niro, GA, Palmieri, VO, Picciotto, A, Podda, M, Portincasa, P, Ronca, V, Rosina, F, Rossi, S, Sogno, I, Spinzi, G, Spreafico, M, Strazzabosco, M, Tarallo, S, Tarocchi, M, Tiribelli, C, Toniutto, P, Vinci, M & Cramp, M 2015, 'International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways', Nature Communications, vol. 6, no. 1. https://doi.org/10.1038/ncomms9019

TY - JOUR

T1 - International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

AU - Cordell, Heather J.

AU - Han, Younghun

AU - Mells, George F.

AU - Li, Y

AU - Hirschfield, Gideon M.

AU - Greene, Casey S.

AU - Xie, Gang

AU - Juran, Brian D.

AU - Zhu, Dakai

AU - Qian, David C.

AU - Floyd, James A.B.

AU - Morley, Katherine I.

AU - Prati, Daniele

AU - Lleo, Ana

AU - Cusi, Daniele

AU - Schlicht, Erik M.

AU - Lammert, Craig

AU - Atkinson, Elizabeth J.

AU - Chan, LL

AU - de, Andrade M

AU - Balschun, Tobias

AU - Mason, Andrew L.

AU - Myers, Robert P.

AU - Zhang, Jinyi

AU - Milkiewicz, Piotr

AU - Qu, Jia

AU - Odin, Joseph A.

AU - Luketic, Velimir A.

AU - Bacon, Bruce R.

AU - Bodenheimer, Henry C.

AU - Liakina, Valentina

AU - Vincent, Catherine

AU - Levy, Cynthia

AU - Gregersen, Peter K.

AU - Almasio, Piero L.

AU - Alvaro, Domenico

AU - Andreone, Pietro

AU - Andriulli, Angelo

AU - Barlassina, Cristina

AU - Battezzati, Pier Maria

AU - Benedetti, Antonio

AU - Bernuzzi, Francesca

AU - Bianchi, Ilaria

AU - Bragazzi, Maria Consiglia

AU - Brunetto, Maurizia

AU - Bruno, Savino

AU - Casella, Giovanni

AU - Coco, Barbara

AU - Colli, Agostino

AU - Colombo, M

AU - Colombo, S

AU - Cursaro, Carmela

AU - Crocè, Lory Saveria

AU - Crosignani, Andrea

AU - Donato, Maria Francesca

AU - Elia, Gianfranco

AU - Fabris, Luca

AU - Ferrari, Carlo

AU - Floreani, Annarosa

AU - Foglieni, Barbara

AU - Fontana, Rosanna

AU - Galli, Andrea

AU - Lazzari, Roberta

AU - Macaluso, Fabio

AU - Malinverno, Federica

AU - Marra, Fabio

AU - Marzioni, Marco

AU - Mattalia, Alberto

AU - Montanari, Renzo

AU - Morini, Lorenzo

AU - Morisco, Filomena

AU - Hani, S M

AU - Muratori, L

AU - Muratori, P

AU - Niro, Grazia A.

AU - Palmieri, Vincenzo O.

AU - Picciotto, Antonio

AU - Podda, Mauro

AU - Portincasa, Piero

AU - Ronca, Vincenzo

AU - Rosina, Floriano

AU - Rossi, Sonia

AU - Sogno, Ilaria

AU - Spinzi, Giancarlo

AU - Spreafico, Marta

AU - Strazzabosco, Mario

AU - Tarallo, Sonia

AU - Tarocchi, Mirko

AU - Tiribelli, Claudio

AU - Toniutto, Pierluigi

AU - Vinci, Maria

AU - Cramp, Matthew

PY - 2015/9/22

Y1 - 2015/9/22

N2 - AbstractPrimary 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.

AB - AbstractPrimary 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.

UR - https://pearl.plymouth.ac.uk/pms-research/1730/

U2 - 10.1038/ncomms9019

DO - 10.1038/ncomms9019

M3 - Article

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

Abstract

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