International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways
Authors: 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 ,   Canadian-US PBC Consortium, 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 , Qu Jia , Odin Joseph A , Luketic Velimir A , Bacon Bruce R , Bodenheimer Jr Henry C , Liakina Valentina , Vincent Catherine , Levy Cynthia , Gregersen Peter K ,   Italian PBC Genetics Study Group, Almasio Piero L , Alvaro Domenico , Andreone Pietro , Andriulli Angelo , Barlassina Cristina , Battezzati Pier Maria , Benedetti Antonio , Bernuzzi Francesca , Bianchi Ilaria , Bragazzi Maria Consiglia , Brunetto Maurizia , Bruno Savino , Casella Giovanni , Coco Barbara , Colli Agostino , Colombo Massimo , Colombo Silvia , Cursaro Carmela , Crocè Lory Saveria , Crosignani Andrea , Donato Maria Francesca , 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 , Hani S Mousa , 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 , Vinci Maria , Zuin Massimo ,   UK-PBC Consortium, Ch'ng Chin Lye , Rahman Mesbah , Yapp Tom , Sturgess Richard , Healey Christopher , Czajkowski Marek , Gunasekera Anton , Gyawali Pranab , Premchand Purushothaman , Kapur Kapil , Marley Richard , Foster Graham , Watson Alan , Dias Aruna , Subhani Javaid , Harvey Rory , McCorry Roger , Ramanaden David , Gasem Jaber , Evans Richard , Mathialahan Thiriloganathan , Shorrock Christopher , Lipscomb George , Southern Paul , Tibble Jeremy , Gorard David , Palegwala Altaf , Jones Susan , Carbone Marco , Dawwas Mohamed , Alexander Graeme , Dolwani Sunil , Prince Martin , Foxton Matthew , Elphick David , Mitchison Harriet , Gooding Ian , Karmo Mazn , Saksena Sushma , Mendall Mike , Patel Minesh , Ede Roland , Austin Andrew , Sayer Joanna , Hankey Lorraine , Hovell Christopher , Fisher Neil , Carter Martyn , Koss Konrad , Piotrowicz Andrzej , Grimley Charles , Neal David , Lim Guan , Levi Sass , Ala Aftab , Broad Andrea , Saeed Athar , Wood Gordon , Brown Jonathan , Wilkinson Mark , Gordon Harriet , Ramage John , Ridpath Jo , Ngatchu Theodore , Grover Bob , Shaukat Syed , Shidrawi Ray , Abouda George , Ali Faiz , Rees Ian , Salam Imroz , Narain Mark , Brown Ashley , Taylor-Robinson Simon , Williams Simon , Grellier Leonie , Banim Paul , Das Debashis , Chilton Andrew , Heneghan Michael , Curtis Howard , Gess Markus , Drake Ian , Aldersley Mark , Davies Mervyn , Jones Rebecca , McNair Alastair , Srirajaskanthan Raj , Pitcher Maxton , Sen Sambit , Bird George , Barnardo Adrian , Kitchen Paul , Yoong Kevin , Chirag Oza , Sivaramakrishnan Nurani , MacFaul George , Jones David , Shah Amir , Evans Chris , Saha Subrata , Pollock Katharine , Bramley Peter , Mukhopadhya Ashis , Fraser Andrew , Mills Peter , Shallcross Christopher , Campbell Stewart , Bathgate Andrew , Shepherd Alan , Dillon John , Rushbrook Simon , Przemioslo Robert , Macdonald Christopher , Metcalf Jane , Shmueli Udi , Davis Andrew , Naqvi Asifabbas , Lee Tom , Ryder Stephen D , Collier Jane , Klass Howard , Ninkovic Mary , Cramp Matthew , Sharer Nicholas , Aspinall Richard , Goggin Patrick , Ghosh Deb , Douds Andrew , Hoeroldt Barbara , Booth Jonathan , Williams Earl , Hussaini Hyder , Stableforth William , Ayres Reuben , Thorburn Douglas , Marshall Eileen , Burroughs Andrew , Mann Steven , Lombard Martin , Richardson Paul , Patanwala Imran , Maltby Julia , Brookes Matthew , Mathew Ray , Vyas Samir , Singhal Saket , Gleeson Dermot , Misra Sharat , Butterworth Jeff , George Keith , Harding Tim , Douglass Andrew , Panter Simon , Shearman Jeremy , Bray Gary , Butcher Graham , Forton Daniel , Mclindon John , Cowan Matthew , Whatley Gregory , Mandal Aditya , Gupta Hemant , Sanghi Pradeep , Jain Sanjiv , Pereira Steve , Prasad Geeta , Watts Gill , Wright Mark , Neuberger James , Gordon Fiona , Unitt Esther , Grant Allister , Delahooke Toby , Higham Andrew , Brind Alison , Cox Mark , Ramakrishnan Subramaniam , King Alistair , Collins Carole , Whalley Simon , Li Andy , Fraser Jocelyn , Bell Andrew , Wong Voi Shim , Singhal Amit , Gee Ian , Ang Yeng , Ransford Rupert , Gotto James , Millson Charles , Bowles Jane , Thomas Caradog , Harrison Melanie , Galaska Roman , Kendall Jennie , Whiteman Jessica , Lawlor Caroline , Gray Catherine , Elliott Keith , Mulvaney-Jones Caroline , Hobson Lucie , Van Duyvenvoorde Greta , Loftus Alison , Seward Katie , Penn Ruth , Maiden Jane , Damant Rose , Hails Janeane , Cloudsdale Rebecca , Silvestre Valeria , Glenn Sue , Dungca Eleanor , Wheatley Natalie , Doyle Helen , Kent Melanie , Hamilton Caroline , Braim Delyth , Wooldridge Helen , Abrahams Rachel , Paton Alison , Lancaster Nicola , Gibbins Andrew , Hogben Karen , Desousa Phillipa , Muscariu Florin , Musselwhite Janine , McKay Alexandra , Tan LaiTing , Foale Carole , Brighton Jacqueline , Flahive Kerry , Nambela Estelle , Townshend Paula , Ford Chris , Holder Sophie , Palmer Caroline , Featherstone James , Nasseri Mariam , Sadeghian Joy , Williams Bronwen , Thomas Carol , Rolls Sally-Ann , Hynes Abigail , Duggan Claire , Jones Sarah , Crossey Mary , Stansfield Glynis , MacNicol Carolyn , Wilkins Joy , Wilhelmsen Elva , Raymode Parizade , Lee Hye-Jeong , Durant Emma , Bishop Rebecca , Ncube Noma , Tripoli Sherill , Casey Rebecca , Cowley Caroline , Miller Richard , Houghton Kathryn , Ducker Samantha , Wright Fiona , Bird Bridget , Baxter Gwen , Keggans Janie , Hughes Maggie , Grieve Emma , Young Karin , Williams D , Ocker Kate , Hines Frances , Martin Kirsty , Innes Caron , Valliani Talal , Fairlamb Helen , Thornthwaite Sarah , Eastick Anne , Tanqueray Elizabeth , Morrison Jennifer , Holbrook Becky , Browning Julie , Walker Kirsten , Congreave Susan , Verheyden Juliette , Slininger Susan , Stafford Lizzie , O'Donnell Denise , Ainsworth Mark , Lord Susan , Kent Linda , March Linda , Dickson Christine , Simpson Diane , Longhurst Beverley , Hayes Maria , Shpuza Ervin , White Nikki , Besley Sarah , Pearson Sallyanne , Wright Alice , Jones Linda , Gunter Emma , Dewhurst Hannah , Fouracres Anna , Farrington Liz , Graves Lyn , Marriott Suzie , Leoni Marina , Tyrer David , Martin Kate , Dali-kemmery Lola , Lambourne Victoria , Green Marie , Sirdefield Dawn , Amor Kelly , Colley Julie , Shinder Bal , Jones Jayne , Mills Marisa , Carnahan Mandy , Taylor Natalie , Boulton Kerenza , Tregonning Julie , Brown Carly , Clifford Gayle , Archer Emily , Hamilton Maria , Curtis Janette , Shewan Tracey , Walsh Sue , Warner Karen , Netherton Kimberley , Mupudzi Mcdonald , Gunson Bridget , Gitahi Jane , Gocher Denise , Batham Sally , Pateman Hilary , Desmennu Senayon , Conder Jill , Clement Darren , Gallagher Susan , Orpe Jacky , Chan PuiChing , Currie Lynn , O'Donohoe Lynn , Oblak Metod , Morgan Lisa , Quinn Marie , Amey Isobel , Baird Yolanda , Cotterill Donna , Cumlat Lourdes , Winter Louise , Greer Sandra , Spurdle Katie , Allison Joanna , Dyer Simon , Sweeting Helen , Kordula Jean , Gershwin M. Eric , Anderson Carl A. , Lazaridis Konstantinos N. , Invernizzi Pietro , Seldin Michael F. , Sandford Richard N. , Amos Christopher I. , Siminovitch Katherine A. 
Published: September 2015

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.