6533b860fe1ef96bd12c2c15

RESEARCH PRODUCT

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

Heather J. CordellHan YounghunGeorge F. MellsLi YafangGideon M. HirschfieldCasey S. GreeneXie GangBrian D. Juran 72 Dakai ZhuDavid C. Qian 2James A. B. FloydKatherine I. Morley Daniele Prati 11 Ana Lleo 12Cusi DanieleM. Eric Gershwin 15Carl A. Anderson 8Konstantinos N. Lazaridis 7Invernizzi PietroMichael F. Seldin 15Richard N. SandfordChristopher I. Amos 2Katherine A. SiminovitchErik M. Schlicht 77 Craig LammertElizabeth J. Atkinson 19Landon L. Chan 19 Mariza De Andrade 19 Tobias Balschun 20Andrew L. Mason 21Robert P. Myers 22 Jinyi Zhang 23 Piotr Milkiewicz 24 Jia Qu 25Joseph A. Odin 26Velimir A. Luketic 27Bruce R. Bacon 28Henry C. Bodenheimer Jr 29 Valentina Liakina 30 Catherine Vincent 31 Cynthia Levy 32Peter K. Gregersen33 Piero L. Almasio Domenico Alvaro 35 Pietro Andreone 36 Angelo Andriulli 37 Cristina Barlassina 38 Pier Maria Battezzati 39 Antonio Benedetti 40 Francesca Bernuzzi 41 Ilaria Bianchi 41 Maria Consiglia Bragazzi 42 Maurizia Brunetto 43 Savino Bruno 41 Giovanni Casella 44 Barbara Coco 43 Agostino Colli 45 Massimo Colombo 46 Silvia Colombo 47 Carmela Cursaro 36` 48 Lory Saveria Croce Andrea Crosignani 39 Maria Francesca Donato 46 Gianfranco Elia 49 Luca Fabris 50 Carlo Ferrari 49 Annarosa Floreani 51 Barbara Foglieni 11 Rosanna Fontana 37Andrea Galli Roberta Lazzari 51 Fabio Macaluso 34 Federica Malinverno 46Fabio Marra Marco Marzioni 40 Alberto Mattalia 54 Renzo Montanari 55 Lorenzo Morini 56 Filomena Morisco 5741 Mousa Hani S. Luigi Muratori 36 Paolo Muratori 36Grazia A. Niro 37Vincenzo O. Palmieri 58 Antonio Picciotto 59 Mauro Podda 41 Piero Portincasa 58 Vincenzo Ronca 41 Floriano Rosina 60 Sonia Rossi 41 Ilaria Sogno 41 Giancarlo Spinzi 61 Marta Spreafico 11Strazzabosco Mario Sonia Tarallo 60Mirko Tarocchi Claudio Tiribelli 48 Pierluigi Toniutto 64 Maria Vinci 65Zuin Massimo Chin Lye Ch’ng Mesbah Rahman 68 Tom Yapp 69 Richard Sturgess 70 Christopher Healey 71Czajkowski MarekGunasekera Anton Pranab Gyawali 77 Purushothaman Premchand 78 Kapil Kapur 79 Richard Marley 80 Graham Foster 80 Alan Watson 81 Aruna Dias 82 Javaid Subhani 83 Rory Harvey 84 Roger Mccorry 85 David Ramanaden 86 Jaber Gasem 87 Richard Evans 88 Thiriloganathan Mathialahan 89 Christopher Shorrock 90 George Lipscomb 91 Paul Southern 92 Jeremy Tibble 93 94Gorard David Altaf Palegwala 98Jones Susan Marco Carbone 101 Mohamed Dawwas 101 Graeme Alexander 101Dolwani Sunil Martin Prince 104 Matthew Foxton 105 David Elphick 106 Harriet Mitchison 107 Ian Gooding 108 Mazn Karmo 109Saksena SushmaMendall MikePatel MineshEde Roland Andrew Austin 119Sayer Joanna Lorraine Hankey 122 Christopher Hovell 122 Neil Fisher 123Carter Martyn Konrad Koss 126Piotrowicz AndrzejGrimley CharlesNeal David Guan Lim 135Levi Sass Aftab Ala 138 Andrea Broad 139 Athar Saeed 139 Gordon Wood 140Brown JonathanWilkinson Mark Harriet Gordon 145 John Ramage 146 Jo Ridpath 147Ngatchu Theodore Bob Grover 151 Syed Shaukat 152 Ray Shidrawi 153Abouda George Faiz Ali 156 Ian Rees 157 Imroz Salam 158 Mark Narain 159Brown Ashley Simon Taylor Robinson 162 Simon Williams 163 Leonie Grellier 164 Paul Banim 165 Debasish Das 166 Andrew Chilton 166 Michael Heneghan 167Curtis Howard Markus Gess 170Drake IanAldersley MarkDavies MervynJones Rebecca Alastair Mcnair 175 Raj Srirajaskanthan 176Pitcher Maxton Sambit Sen 179Bird George Adrian Barnardo 182 Paul Kitchen 182 Kevin Yoong 183Chirag Oza Nurani Sivaramakrishnan 186 George Macfaul 187 David Jones 188 Amir Shah 189 Chris Evans 190 Subrata Saha 191Pollock KatharineBramley PeterMukhopadhya AshisFraser AndrewMills PeterShallcross ChristopherCampbell StewartBathgate Andrew Alan Shepherd 213 John Dillon 214 Simon Rushbrook 215 Robert Przemioslo 216 Christopher MacdonaldMetcalf Jane Udi Shmueli 221Davis AndrewNaqvi AsifabbasLee TomStephen D. Ryder Jane Collier 231Klass HowardNinkovic Mary Matthew Cramp 238 Nicholas Sharer 239 Richard Aspinall 240 Patrick Goggin 240Ghosh Deb Andrew Douds 243 Barbara Hoeroldt 244 Jonathan Booth 245 Earl Williams 246 Hyder Hussaini 247 William Stableforth 247 Reuben Ayres 248 Douglas Thorburn 249 Eileen Marshall 249 Andrew Burroughs 249Mann Steven Martin Lombard 252 Paul Richardson 252 Imran Patanwala 252 Julia Maltby 253 Matthew Brookes 254Mathew Ray Samir Vyas 257 Saket Singhal 258Gleeson DermotMisra SharatButterworth Jeff Keith George 265Harding TimDouglass Andrew Simon Panter 270 Jeremy Shearman 271 Gary Bray 272Butcher Graham Daniel Forton 275Mclindon John Matthew Cowan 279 Gregory Whatley 280Mandal AdityaGupta HemantSanghi Pradeep Sanjiv Jain 283 Steve Pereira 284 Geeta Prasad 285 Gill Watts 285 Mark Wright 286 James Neuberger 287 Fiona Gordon 288 Esther Unitt 289Grant AllisterDelahooke Toby Andrew Higham 293 Alison Brind 294 Mark Cox 295 Subramaniam Ramakrishnan 296King Alistair Carole Collins 300Whalley Simon Andy Li 303 Jocelyn Fraser 304 Andrew Bell 305 Voi Shim Wong 306Singhal AmitGee Ian Yeng Ang 312 Rupert Ransford 313 James Gotto 314Millson Charles Jane Bowles 318Thomas Caradog Melanie Harrison 70 Roman Galaska 71Kendall JennieWhiteman JessicaLawlor CarolineGray Catherine Keith Elliott 79 Caroline Mulvaney JonesHobson Lucie Greta Van Duyvenvoorde 90 Alison Loftus 91 Katie Seward 92Penn Ruth Jane Maiden 98 Rose Damant 98 Janeane Hails 101Cloudsdale Rebecca Valeria Silvestre 105 Sue Glenn 106 Eleanor Dungca 107 Natalie Wheatley 108 Helen Doyle 109Kent MelanieHamilton CarolineBraim Delyth Helen Wooldridge 117 Rachel Abrahams 117 Alison Paton 119Lancaster Nicola Andrew Gibbins 122 Karen Hogben 122Desousa PhillipaMuscariu FlorinMusselwhite Janine Alexandra Mckay 132 Laiting Tan 135 Carole Foale 138 Jacqueline Brighton 138 Kerry Flahive 140Nambela EstelleTownshend PaulaFord ChrisHolder SophiePalmer Caroline James Featherstone 147 Mariam Nasseri 151 Joy Sadeghian 153Williams Bronwen Carol Thomas 156 Sally Ann Rolls 156 Abigail Hynes 159 Claire Duggan 159 Sarah Jones 159Crossey Mary Glynis Stansfield 163 Carolyn Macnicol 163 Joy Wilkins 164 Elva Wilhelmsen 165 Parizade Raymode 166 Hye Jeong Lee 167Durant EmmaBishop RebeccaNcube NomaTripoli SherillCasey Rebecca Caroline Cowley 182 Richard Miller 183 Kathryn Houghton 188 Samantha Ducker 188 Fiona Wright 189 Bridget Bird 191 Gwen Baxter 191 Janie Keggans 191Hughes Maggie Emma Grieve 196 Karin Young 196D. Williams 197 Kate Ocker 199Hines FrancesMartin KirstyInnes Caron Talal Valliani 216Fairlamb HelenThornthwaite SarahEastick Anne Elizabeth Tanqueray 221 Jennifer Morrison 222 Becky Holbrook 222Browning JulieWalker KirstenCongreave SusanVerheyden JulietteSlininger Susan Lizzie Stafford 231 Denise O’donnell 231 Mark Ainsworth 231 Susan Lord 118Kent Linda Linda March 238 Christine Dickson 239 Diane Simpson 239 Beverley Longhurst 240 Maria Hayes 240Shpuza ErvinWhite NikkiBesley Sarah Sallyanne Pearson 244 Alice Wright 245 Linda Jones 245 Emma Gunter 246 Hannah Dewhurst 246 Anna Fouracres 247 Liz Farrington 247 Lyn Graves 247 Suzie Marriott 248 Marina Leoni 249 David Tyrer 252 Kate Martin 252 Lola Dali Kemmery 253 Victoria Lambourne 253 Marie Green 254Sirdefield Dawn Kelly Amor 255 Julie Colley 258 Bal Shinder 258 Jayne Jones 260 Marisa Mills 260Carnahan Mandy Natalie Taylor 265 Kerenza Boulton 265Tregonning Julie Carly Brown 270 Gayle Clifford 270 Emily Archer 271Hamilton Maria Janette Curtis 278 Tracey Shewan 279 Sue Walsh 280Warner Karen Kimberley Netherton 283 Mcdonald Mupudzi 286 Bridget Gunson 287 Jane Gitahi 288 Denise Gocher 289Batham SallyPateman HilaryDesmennu Senayon Jill Conder 293 Darren Clement 294 Susan Gallagher 294 Jacky Orpe 256 Puiching Chan 296Currie LynnO’donohoe Lynn Metod Oblak 300 Lisa Morgan 302 Marie Quinn 303 Isobel Amey 304 Yolanda Baird 304 Donna Cotterill 305 Lourdes Cumlat 306 Louise Winter 312 Sandra Greer 312Spurdle KatieAllison JoannaDyer SimonSweeting HelenKordula Jean

subject

Liver CirrhosisGenetics and Molecular Biology (all)pathogenesirisk assessment EMTREE medical terms: Articlegenetic associationgenotypeEMTREE drug terms: chemokine receptor CCR6genetic riskBiochemistrymeta-analysiprimary biliary cirrhosichemokine receptor CCR6 [EMTREE drug terms]single nucleotide polymorphismgenetic variabilityArticle [risk assessment EMTREE medical terms]Liver Cirrhosis BiliarypathogenesisBiliaryChemistry (all)STAT protein GEOBASE Subject Index: disease treatmentcohort analysisgenome wide meta analysis PBCsignal transductiongene locuscohort analysiCBPArticle*Physics and Astronomy (all)macrophage inflammatory protein 3alphaHumanscontrolled studyhumaninterleukin 27genomeBiochemistry Genetics and Molecular Biology (all)meta analysiinterleukin 12p40EMTREE drug terms: chemokine receptor CCR6; interleukin 12; interleukin 12p40; interleukin 27; Janus kinase; macrophage inflammatory protein 3alpha; STAT protein GEOBASE Subject Index: disease treatment; genome; meta-analysis; pathogen; risk assessment EMTREE medical terms: Article; cohort analysis; controlled study; gene locus; genetic association; genetic predisposition; genetic risk; genetic variability; genotype; human; major clinical study; meta analysis; pathogenesis; primary biliary cirrhosis; signal transduction; single nucleotide polymorphismmajor clinical studyprimary biliary cirrhosismeta-analysisdisease treatment [STAT protein GEOBASE Subject Index]Biochemistry Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)Humans; Liver Cirrhosis; Biliary; Genome-Wide Association Study; Biochemistry; Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)gene locuinterleukin 12genetic predispositionJanus kinasepathogenmeta analysisHumans; Liver Cirrhosis Biliary; Genome-Wide Association Study; Biochemistry Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)Genome-Wide Association Study

description

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.

yearjournalcountryeditionlanguage
2015-01-30
10.1038/ncomms9019http://hdl.handle.net/11568/844124