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

Heather J. Cordell, Younghun Han, George F. Mells, Yafang 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, M. Eric Gershwin, Carl A. Anderson, Konstantinos N. Lazaridis, Pietro Invernizzi, Michael F SeldinRichard N. Sandford, Christopher I. Amos, Katherine A. Siminovitch, Erik M. Schlicht, Craig Lammert, Elizabeth J. Atkinson, Landon L. Chan, Mariza De Andrade, 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, Massimo Colombo, Silvia 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. Mousa Hani, Luigi Muratori, Paolo 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, Massimo Zuin, Chin Lye Ch'Ng, Mesbah Rahman, Tom Yapp, Richard Sturgess, Christopher Healey, Marek Czajkowski, Anton Gunasekera, Pranab Gyawali, Purushothaman Premchand, Kapil Kapur, Richard Marley, Graham Foster, Alan Watson, Aruna Dias, Javaid Subhani, Rory Harvey, Roger McCorry, David Ramanaden, Jaber Gasem, Richard Evans, Thiriloganathan Mathialahan, Christopher Shorrock, George Lipscomb, Paul Southern, Jeremy Tibble, David Gorard, Altaf Palegwala, Susan Jones, Marco Carbone, Mohamed Dawwas, Graeme Alexander, Sunil Dolwani, Martin Prince, Matthew Foxton, David Elphick, Harriet Mitchison, Ian Gooding, Mazn Karmo, Sushma Saksena, Mike Mendall, Minesh Patel, Roland Ede, Andrew Austin, Joanna Sayer, Lorraine Hankey, Christopher Hovell, Neil Fisher, Martyn Carter, Konrad Koss, Andrzej Piotrowicz, Charles Grimley, David Neal, Guan Lim, Sass Levi, Aftab Ala, Andrea Broad, Athar Saeed, Gordon Wood, Jonathan Brown, Mark Wilkinson, Harriet Gordon, John Ramage, Jo Ridpath, Theodore Ngatchu, Bob Grover, Syed Shaukat, Ray Shidrawi, George Abouda, Faiz Ali, Ian Rees, Imroz Salam, Mark Narain, Ashley Brown, Simon Taylor-Robinson, Simon Williams, Leonie Grellier, Paul Banim, Debasish Das, Andrew Chilton, Michael Heneghan, Howard Curtis, Markus Gess, Ian Drake, Mark Aldersley, Mervyn Davies, Rebecca Jones, Alastair McNair, Raj Srirajaskanthan, Maxton Pitcher, Sambit Sen, George Bird, Adrian Barnardo, Paul Kitchen, Kevin Yoong, Oza Chirag, Nurani Sivaramakrishnan, George MacFaul, David Jones, Amir Shah, Chris Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Andrew Fraser, Peter Mills, Christopher Shallcross, Stewart Campbell, Andrew Bathgate, Alan Shepherd, John Dillon, Simon Rushbrook, Robert Przemioslo, Christopher Macdonald, Jane Metcalf, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom Lee, Dyder Stephen, Jane Collier, Howard Klass, Mary Ninkovic, Matthew Cramp, Nicholas Sharer, Richard Aspinall, Patrick Goggin, Deb Ghosh, Andrew Douds, Barbara Hoeroldt, Jonathan Booth, Earl Williams, Hyder Hussaini, William Stableforth, Reuben Ayres, Douglas Thorburn, Eileen Marshall, Andrew Burroughs, Steven Mann, Martin Lombard, Paul Richardson, Imran Patanwala, Julia Maltby, Matthew Brookes, Ray Mathew, Samir Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Simon Panter, Jeremy Shearman, Gary Bray, Graham Butcher, Daniel Forton, John McLindon, Matthew Cowan, Gregory Whatley, Aditya Mandal, Hemant Gupta, Pradeep Sanghi, Sanjiv Jain, Steve Pereira, Geeta Prasad, Gill Watts, Mark Wright, James Neuberger, Fiona Gordon, Esther Unitt, Allister Grant, Toby Delahooke, Andrew Higham, Alison Brind, Mark Cox, Subramaniam Ramakrishnan, Alistair King, Carole Collins, Simon Whalley, Andy Li, Jocelyn Fraser, Andrew Bell, Voi Shim Wong, Amit Singhal, Ian Gee, Yeng Ang, Rupert Ransford, James Gotto, Charles Millson, Jane Bowles, Caradog Thomas, Melanie Harrison, Roman Galaska, Jennie Kendall, Jessica Whiteman, Caroline Lawlor, Catherine Gray, Keith Elliott, Caroline Mulvaney-Jones, Lucie Hobson, Greta Van Duyvenvoorde, Alison Loftus, Katie Seward, Ruth Penn, Jane Maiden, Rose Damant, Janeane Hails, Rebecca Cloudsdale, Valeria Silvestre, Sue Glenn, Eleanor Dungca, Natalie Wheatley, Helen Doyle, Melanie Kent, Caroline Hamilton, Delyth Braim, Helen Wooldridge, Rachel Abrahams, Alison Paton, Nicola Lancaster, Andrew Gibbins, Karen Hogben, Phillipa Desousa, Florin Muscariu, Janine Musselwhite, Alexandra McKay, Laiting Tan, Carole Foale, Jacqueline Brighton, Kerry Flahive, Estelle Nambela, Paula Townshend, Chris Ford, Sophie Holder, Caroline Palmer, James Featherstone, Mariam Nasseri, Joy Sadeghian, Bronwen Williams, Carol Thomas, Sally Ann Rolls, Abigail Hynes, Claire Duggan, Sarah Jones, Mary Crossey, Glynis Stansfield, Carolyn MacNicol, Joy Wilkins, Elva Wilhelmsen, Parizade Raymode, Hye Jeong Lee, Emma Durant, Rebecca Bishop, Noma Ncube, Sherill Tripoli, Rebecca Casey, Caroline Cowley, Richard Miller, Kathryn Houghton, Samantha Ducker, Fiona Wright, Bridget Bird, Gwen Baxter, Janie Keggans, Maggie Hughes, Emma Grieve, Karin Young, D. Williams, Kate Ocker, Frances Hines, Kirsty Martin, Caron Innes, Talal Valliani, Helen Fairlamb, Sarah Thornthwaite, Anne Eastick, Elizabeth Tanqueray, Jennifer Morrison, Becky Holbrook, Julie Browning, Kirsten Walker, Susan Congreave, Juliette Verheyden, Susan Slininger, Lizzie Stafford, Denise O'Donnell, Mark Ainsworth, Susan Lord, Linda Kent, Linda March, Christine Dickson, Diane Simpson, Beverley Longhurst, Maria Hayes, Ervin Shpuza, Nikki White, Sarah Besley, Sallyanne Pearson, Alice Wright, Linda Jones, Emma Gunter, Hannah Dewhurst, Anna Fouracres, Liz Farrington, Lyn Graves, Suzie Marriott, Marina Leoni, David Tyrer, Kate Martin, Lola Dali-Kemmery, Victoria Lambourne, Marie Green, Dawn Sirdefield, Kelly Amor, Julie Colley, Bal Shinder, Jayne Jones, Marisa Mills, Mandy Carnahan, Natalie Taylor, Kerenza Boulton, Julie Tregonning, Carly Brown, Gayle Clifford, Emily Archer, Maria Hamilton, Janette Curtis, Tracey Shewan, Sue Walsh, Karen Warner, Kimberley Netherton, McDonald Mupudzi, Bridget Gunson, Jane Gitahi, Denise Gocher, Sally Batham, Hilary Pateman, Senayon Desmennu, Jill Conder, Darren Clement, Susan Gallagher, Jacky Orpe, Puiching Chan, Lynn Currie, Lynn O'Donohoe, Metod Oblak, Lisa Morgan, Marie Quinn, Isobel Amey, Yolanda Baird, Donna Cotterill, Lourdes Cumlat, Louise Winter, Sandra Greer, Katie Spurdle, Joanna Allison, Simon Dyer, Helen Sweeting, Jean Kordula

Research output: Contribution to journalArticle

105 Scopus citations

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

Original languageEnglish (US)
Article number8019
JournalNature Communications
Volume6
DOIs
StatePublished - Sep 22 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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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., Gershwin, M. E., Anderson, C. A., Lazaridis, K. N., Invernizzi, P., ... Kordula, J. (2015). International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways. Nature Communications, 6, [8019]. https://doi.org/10.1038/ncomms9019