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1. Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis

Author

Mells, George F, Floyd, James AB, Morley, Katherine I, Cordell, Heather J, Franklin, Christopher S, Shin, So-Youn, Heneghan, Michael A, Neuberger, James M, Donaldson, Peter T, Day, Darren B, Ducker, Samantha J, Muriithi, Agnes W, Wheater, Elizabeth F, Hammond, Christopher J, Dawwas, Muhammad F, UK PBC Consortium, Wellcome Trust Case Control Consortium 3, Jones, David E, Peltonen, Leena, Alexander, Graeme J, Sandford, Richard N, and Anderson, Carl A

Subjects
Male, Receptors, CXCR5, Death Domain Receptor Signaling Adaptor Proteins, Receptors, Interleukin-7, Monosaccharide Transport Proteins, Liver Cirrhosis, Biliary, NF-kappa B p50 Subunit, Adaptive Immunity, STAT4 Transcription Factor, Polymorphism, Single Nucleotide, Immunity, Innate, Linkage Disequilibrium, Cohort Studies, Receptors, Tumor Necrosis Factor, Type I, Risk Factors, Case-Control Studies, Databases, Genetic, B7-1 Antigen, Guanine Nucleotide Exchange Factors, Humans, Female, Genetic Predisposition to Disease, Lectins, C-Type, Genome-Wide Association Study
Abstract

In addition to the HLA locus, six genetic risk factors for primary biliary cirrhosis (PBC) have been identified in recent genome-wide association studies (GWAS). To identify additional loci, we carried out a GWAS using 1,840 cases from the UK PBC Consortium and 5,163 UK population controls as part of the Wellcome Trust Case Control Consortium 3 (WTCCC3). We followed up 28 loci in an additional UK cohort of 620 PBC cases and 2,514 population controls. We identified 12 new susceptibility loci (at a genome-wide significance level of P < 5 × 10⁻⁸) and replicated all previously associated loci. We identified three further new loci in a meta-analysis of data from our study and previously published GWAS results. New candidate genes include STAT4, DENND1B, CD80, IL7R, CXCR5, TNFRSF1A, CLEC16A and NFKB1. This study has considerably expanded our knowledge of the genetic architecture of PBC.

Published
2020
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2. Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis

Author

Liu, Jimmy Z, Almarri, Mohamed A, Gaffney, Daniel J, Mells, George F, Jostins, Luke, Cordell, Heather J, Ducker, Samantha J, Day, Darren B, Heneghan, Michael A, Neuberger, James M, Donaldson, Peter T, Bathgate, Andrew J, Burroughs, Andrew, Davies, Mervyn H, Jones, David E, Alexander, Graeme J, Barrett, Jeffrey C, Sandford, Richard N, Anderson, Carl A, UK Primary Biliary Cirrhosis (PBC) Consortium, Wellcome Trust Case Control Consortium 3, Sandford, Richard [0000-0002-7437-0560], and Apollo - University of Cambridge Repository

Subjects
TYK2 Kinase, Genotype, Liver Cirrhosis, Biliary, Intracellular Signaling Peptides and Proteins, Chromosome Mapping, Proteins, Sequence Analysis, DNA, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Gene Frequency, Genetic Loci, HLA Antigens, Case-Control Studies, Humans, Regression Analysis, Genetic Predisposition to Disease, Chromosomes, Human, Pair 19, Adaptor Proteins, Signal Transducing, Genome-Wide Association Study
Abstract

We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 loci newly associated with PBC (at P0.8) with the most associated variant at the locus. We found multiple independent common, low-frequency and rare variant association signals at five loci. Of the 26 independent non-human leukocyte antigen (HLA) signals tagged on the Immunochip, 15 have SNPs in B-lymphoblastoid open chromatin regions in high LD (r2>0.8) with the most associated variant. This study shows how data from dense fine-mapping arrays coupled with functional genomic data can be used to identify candidate causal variants for functional follow-up.

Published
2012

3. Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis

Author

Mells, George F, Floyd, James AB, Morley, Katherine I, Cordell, Heather J, Franklin, Christopher S, Shin, So-Youn, Heneghan, Michael A, Neuberger, James M, Donaldson, Peter T, Day, Darren B, Ducker, Samantha J, Muriithi, Agnes W, Wheater, Elizabeth F, Hammond, Christopher J, Dawwas, Muhammad F, UK PBC Consortium, Wellcome Trust Case Control Consortium 3, Jones, David E, Peltonen, Leena, Alexander, Graeme J, Sandford, Richard N, Anderson, Carl A, Sandford, Richard [0000-0002-7437-0560], and Apollo - University of Cambridge Repository

Subjects
Male, Receptors, CXCR5, Death Domain Receptor Signaling Adaptor Proteins, Receptors, Interleukin-7, Monosaccharide Transport Proteins, Liver Cirrhosis, Biliary, NF-kappa B p50 Subunit, Adaptive Immunity, STAT4 Transcription Factor, Polymorphism, Single Nucleotide, Immunity, Innate, Linkage Disequilibrium, Cohort Studies, Receptors, Tumor Necrosis Factor, Type I, Risk Factors, Case-Control Studies, Databases, Genetic, B7-1 Antigen, Guanine Nucleotide Exchange Factors, Humans, Female, Genetic Predisposition to Disease, Lectins, C-Type, Genome-Wide Association Study
Abstract

In addition to the HLA locus, six genetic risk factors for primary biliary cirrhosis (PBC) have been identified in recent genome-wide association studies (GWAS). To identify additional loci, we carried out a GWAS using 1,840 cases from the UK PBC Consortium and 5,163 UK population controls as part of the Wellcome Trust Case Control Consortium 3 (WTCCC3). We followed up 28 loci in an additional UK cohort of 620 PBC cases and 2,514 population controls. We identified 12 new susceptibility loci (at a genome-wide significance level of P < 5 × 10⁻⁸) and replicated all previously associated loci. We identified three further new loci in a meta-analysis of data from our study and previously published GWAS results. New candidate genes include STAT4, DENND1B, CD80, IL7R, CXCR5, TNFRSF1A, CLEC16A and NFKB1. This study has considerably expanded our knowledge of the genetic architecture of PBC.

Published
2011

4. Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis

Author

Liu, Jimmy Z, Almarri, Mohamed A, Gaffney, Daniel J, Mells, George F, Jostins, Luke, Cordell, Heather J, Ducker, Samantha J, Day, Darren B, Heneghan, Michael A, Neuberger, James M, Donaldson, Peter T, Bathgate, Andrew J, Burroughs, Andrew, Davies, Mervyn H, Jones, David E, Alexander, Graeme J, Barrett, Jeffrey C, Sandford, Richard N, Anderson, Carl A, UK Primary Biliary Cirrhosis (PBC) Consortium, and Wellcome Trust Case Control Consortium 3

Subjects
TYK2 Kinase, Genotype, Liver Cirrhosis, Biliary, Intracellular Signaling Peptides and Proteins, Chromosome Mapping, Proteins, Sequence Analysis, DNA, Polymorphism, Single Nucleotide, Linkage Disequilibrium, 3. Good health, Gene Frequency, Genetic Loci, HLA Antigens, Case-Control Studies, Humans, Regression Analysis, Genetic Predisposition to Disease, Chromosomes, Human, Pair 19, Adaptor Proteins, Signal Transducing, Genome-Wide Association Study
Abstract

We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 loci newly associated with PBC (at P0.8) with the most associated variant at the locus. We found multiple independent common, low-frequency and rare variant association signals at five loci. Of the 26 independent non-human leukocyte antigen (HLA) signals tagged on the Immunochip, 15 have SNPs in B-lymphoblastoid open chromatin regions in high LD (r2>0.8) with the most associated variant. This study shows how data from dense fine-mapping arrays coupled with functional genomic data can be used to identify candidate causal variants for functional follow-up.

5. Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score

Author

Marco Carbone, Alessandra Nardi, Steve Flack, Guido Carpino, Nikoletta Varvaropoulou, Caius Gavrila, Ann Spicer, Jonathan Badrock, Francesca Bernuzzi, Vincenzo Cardinale, Holly F Ainsworth, Michael A Heneghan, Douglas Thorburn, Andrew Bathgate, Rebecca Jones, James M Neuberger, Pier Maria Battezzati, Massimo Zuin, Simon Taylor-Robinson, Maria F Donato, John Kirby, Robert Mitchell-Thain, Annarosa Floreani, Fotios Sampaziotis, Luigi Muratori, Domenico Alvaro, Marco Marzioni, Luca Miele, Fabio Marra, Edoardo Giannini, Eugenio Gaudio, Vincenzo Ronca, Giulia Bonato, Laura Cristoferi, Federica Malinverno, Alessio Gerussi, Deborah D Stocken, Heather J Cordell, Gideon M Hirschfield, Graeme J Alexander, Richard N Sandford, David E Jones, Pietro Invernizzi, George F Mells, Caradog Thomas, Meshbah Rahman, Tom Yapp, Chin Lye Ch'ng, Melanie Harrison, Richard Sturgess, Roman Galaska, Chris Healey, Jessica Whiteman, Marek Czaijkowski, Catherine Gray, Anton Gunasekera, Pranab Gyawli, Purushothaman Premchand, Steven Mann, Keith Elliott, Kapil Kapur, Alan Watson, Graham Foster, Paul Trembling, Javaid Subhani, Rory Harvey, Roger McCorry, Carolyn Adgey, Lucie Hobson, Caroline Mulvaney-Jones, Richard Evans, Thiriloganathan Mathialahan, David Ramanaden, Jaber Gasem, Greta Van Duyvenvoorde, Christopher Shorrock, Katie Seward, Paul Southern, Jeremy Tibble, Ruth Penn, David Gorard, Jane Maiden, Rose Damant, Altaf Palegwala, Susan Jones, Graeme Alexander, George Mells, Richard Sandford, Sunil Dolwani, Martin Prince, Valeria Silvestre, Matthew Foxton, Eleanor Dungca, Harriet Mitchison, Natalie Wheatley, Ian Gooding, Helen Doyle, Mazn Karmo, Melanie Kent, Sushma Saksena, Delyth Braim, Minesh Patel, Susan Lord, Roland Ede, Alison Paton, Andrew Austin, Nicola Lancaster, Joanna Sayer, Andrew Gibbins, Karen Hogben, Chris Hovell, Neil Fisher, Martyn Carter, Konrad Koss, Janine Musselwhite, Florin Muscariu, Andrzej Piotreowicz, Alexandra McKay, Charles Grimley, David Neal, Lai Ting Tan, Guan Lim, Jacqueline Brighton, Carole Foale, Aftab Ala, Athar Saeed, Kerry Flahive, Gordon Wood, Paula Townshend, Chris Ford, Jonathan Brown, Jean Kordula, Jane Bowles, Mark Wilkinson, Caroline Palmer, John Ramage, Harriet Gordon, James Featherstone, Jo Ridpath, Theodore Ngatchu, Sass Levi, Syed Shaukat, Joy Sadeghian, Ray Shidrawi, Bronwen Williams, George Abouda, Sarah Jones, Claire Duggan, Abigail Hynes, Mark Narain, Ian Rees, Imroz Salam, Mary Crossey, Ashley Brown, Carolyn MacNicol, Simon Williams, Elva Wilhelmsen, Paul Banim, Parizade Raymode, Andrew Chilton, Debasish Das, Hye-Jeong Lee, Howard Curtis, Michael Heneghan, Markus Gess, Emma Durant, IM Drake, Rebecca Bishop, Mervyn Davies, Mark Aldersley, Noma Ncube, Alistair McNair, Raj Srirajaskanthan, Sambit Sen, Rebecca Casey, George Bird, Mike Mendall, Caroline Cowley, Adrian Barnardo, Paul Kitchen, Kevin Yoong, Kelly Amore, Dawn Sirdefield, Jacky Orpe, Ray Mathew, George MacFaul, Aruna Wrigth, Amir Shah, Chris Evans, Janie Keggans, Bridget Bird, Gwen Baxter, Subrata Saha, Katharine Pollock, Maggie Hughes, Peter Bramley, Emma Grieve, Karin Young, Andrew Fraser, Ashis Mukhopadhya, Kate Ocker, Peter Mills, Francis Hines, Chris Shallcross, Joy Wilkins, Leonie Grellier, Stewart Campbell, Kirsty Martin, Caron Innes, Alan Shepherd, Simon Rushbrook, Talal Valliani, Robert Przemioslo, Helen Fairlamb, Chris Macdonald, Anne Eastick, Jane Metcalf, Elizabeth Tanqueray, Udi Shmueli, Becky Holbrook, Andrew Davis, Julie Browning, Asifabbas Naqvi, Kirsten Walker, Tom Lee, Juliette Verheyden, Susan Slininger, Stephen D Ryder, Roger Chapman, Jane Collier, Denise O'Donnell, Lizzie Stafford, Kate Williamson, Linda Kent, Howard Klass, Mary Ninkovic, Linda March, Matthew Cramp, Diane Simpson, Christine Dickson, Nicholas Sharer, Maria Hayes, Patrick Goggin, Mary Quinne, Sallyanne Pearson, Barbara Hoeroldt, Linda Jones, Alice Wright, Jonathan Booth, Alison Loftus, George Lipscomb, Hannah Dewhurst, Emma Gunter, Earl Williams, Anna Fouracres, Liz Farrington, Lyn Graves, Hyder Hussaini, Bill Stableforth, Suzie Marriott, Reuben Ayres, Marina Leoni, Andrew Burroughs, Eileen Marshall, David Tyrer, Kate Martin, Martin Lombard, Imran Patanwala, Lola Dali-Kemmery, Victoria Lambourne, Julia Maltby, Samir Vyas, Julie Colley, Bal Shinder, Saket Singhal, Jayne Jones, Marisa Mills, Dermot Gleeson, Mandy Carnahan, Jeff Butterworth, Kerenza Boulton, Natalie Taylor, Keith George, Tim Harding, Julie Tregonning, Andrew Douglass, Carly Brown, Gayle Clifford, Simon Panter, Denise Gocher, Jeremy Shearman, Gary Bray, Maria Hamilton, Graham Butcher, Daniel Forton, John Mclindon, Janette Curtis, Debashis Das, Tracey Shewan, Matthew Cowan, Gregory Whatley, Mariam Nasseri, Bob Grover, Nurani Sivaramakrishnan, Samantha Ducker, Kathryn Houghton, David Jones, Laura Griffiths, Sherill Tripoli, Maxton Pitcher, Ervin Shpuza, Nikki White, Deb Ghosh, Andrew Douds, Marie Green, Matthew Brookes, Lourdes Cumlat, Voi Shim Wong, Karen Warner, Kimberley Netherton, Adtya Mandal, Snjiv Jain, Hemant Gupta, Pradeep Sanghi, Steve Pereira, James Neuberger, Bridget Gunson, Gideon Hirschfield, Reina Teegan Lim, Susan Gallagher, Darren Clement, Alison Brind, Gill Watts, Mcdonald Mupudzi, Mark Wright, Jane Gitahi, Fiona Gordon, Denis Gocher, Esther Unitt, Hilary Pateman, Sally Batham, Toby Delahooke, Allister Grant, Jill Conder, Andrew Higham, Mark Cox, Lynn O'Donohoe, Lynn Currie, Alistair King, Metod Oblak, Carole Collins, Simon Whalley, Marie Quinn, Yolanda Baird, Isobel Amey, Jocelyn Fraser, Andy Li, Donna Cotterill, Andrew Bell, Amit Singhal, Ian Gee, Sandra Greer, Yeng Ang, Rupert Ransford, Joanna Allison, James Gotto, Simon Dyer, Helen Sweeting, Charles Millson, Giancarlo Labbadia, Maria Consiglia Bragazzi, Pietro Andreone, Francesco Azzaroli, Andrea Galli, Mirko Tarocchi, Antonio Gasbarrini, Antonio Grieco, Giuseppe Marrone, Maria Francesca Donato, Luca Valenti, Luca Maroni, Cristina Rigamonti, Antonino Picciotto, Carbone, M, Nardi, A, Flack, S, Carpino, G, Varvaropoulou, N, Gavrila, C, Spicer, A, Badrock, J, Bernuzzi, F, Cardinale, V, Ainsworth, H, Heneghan, M, Thorburn, D, Bathgate, A, Jones, R, Neuberger, J, Battezzati, P, Zuin, M, Taylor-Robinson, S, Donato, M, Kirby, J, Mitchell-Thain, R, Floreani, A, Sampaziotis, F, Muratori, L, Alvaro, D, Marzioni, M, Miele, L, Marra, F, Giannini, E, Gaudio, E, Ronca, V, Bonato, G, Cristoferi, L, Malinverno, F, Gerussi, A, Stocken, D, Cordell, H, Hirschfield, G, Alexander, G, Sandford, R, Jones, D, Invernizzi, P, Mells, G, Thomas, C, Rahman, M, Yapp, T, Lye Ch'ng, C, Harrison, M, Sturgess, R, Galaska, R, Healey, C, Whiteman, J, Czaijkowski, M, Gray, C, Gunasekera, A, Gyawli, P, Premchand, P, Mann, S, Elliott, K, Kapur, K, Watson, A, Foster, G, Trembling, P, Subhani, J, Harvey, R, Mccorry, R, Adgey, C, Hobson, L, Mulvaney-Jones, C, Evans, R, Mathialahan, T, Ramanaden, D, Gasem, J, Van Duyvenvoorde, G, Shorrock, C, Seward, K, Southern, P, Tibble, J, Penn, R, Gorard, D, Maiden, J, Damant, R, Palegwala, A, Jones, S, Dolwani, S, Prince, M, Silvestre, V, Foxton, M, Dungca, E, Mitchison, H, Wheatley, N, Gooding, I, Doyle, H, Karmo, M, Kent, M, Saksena, S, Braim, D, Patel, M, Lord, S, Ede, R, Paton, A, Austin, A, Lancaster, N, Sayer, J, Gibbins, A, Hogben, K, Hovell, C, Fisher, N, Carter, M, Koss, K, Musselwhite, J, Muscariu, F, Piotreowicz, A, Mckay, A, Grimley, C, Neal, D, Ting Tan, L, Lim, G, Brighton, J, Foale, C, Ala, A, Saeed, A, Flahive, K, Wood, G, Townshend, P, Ford, C, Brown, J, Kordula, J, Bowles, J, Wilkinson, M, Palmer, C, Ramage, J, Gordon, H, Featherstone, J, Ridpath, J, Ngatchu, T, Levi, S, Shaukat, S, Sadeghian, J, Shidrawi, R, Williams, B, Abouda, G, Duggan, C, Hynes, A, Narain, M, Rees, I, Salam, I, Crossey, M, Brown, A, Macnicol, C, Williams, S, Wilhelmsen, E, Banim, P, Raymode, P, Chilton, A, Das, D, Lee, H, Curtis, H, Gess, M, Durant, E, Drake, I, Bishop, R, Davies, M, Aldersley, M, Ncube, N, Mcnair, A, Srirajaskanthan, R, Sen, S, Casey, R, Bird, G, Mendall, M, Cowley, C, Barnardo, A, Kitchen, P, Yoong, K, Amore, K, Sirdefield, D, Orpe, J, Mathew, R, Macfaul, G, Wrigth, A, Shah, A, Evans, C, Keggans, J, Bird, B, Baxter, G, Saha, S, Pollock, K, Hughes, M, Bramley, P, Grieve, E, Young, K, Fraser, A, Mukhopadhya, A, Ocker, K, Mills, P, Hines, F, Shallcross, C, Wilkins, J, Grellier, L, Campbell, S, Martin, K, Innes, C, Shepherd, A, Rushbrook, S, Valliani, T, Przemioslo, R, Fairlamb, H, Macdonald, C, Eastick, A, Metcalf, J, Tanqueray, E, Shmueli, U, Holbrook, B, Davis, A, Browning, J, Naqvi, A, Walker, K, Lee, T, Verheyden, J, Slininger, S, Ryder, S, Chapman, R, Collier, J, O'Donnell, D, Stafford, L, Williamson, K, Kent, L, Klass, H, Ninkovic, M, March, L, Cramp, M, Simpson, D, Dickson, C, Sharer, N, Hayes, M, Goggin, P, Quinne, M, Pearson, S, Hoeroldt, B, Jones, L, Wright, A, Booth, J, Loftus, A, Lipscomb, G, Dewhurst, H, Gunter, E, Williams, E, Fouracres, A, Farrington, L, Graves, L, Hussaini, H, Stableforth, B, Marriott, S, Ayres, R, Leoni, M, Burroughs, A, Marshall, E, Tyrer, D, Lombard, M, Patanwala, I, Dali-Kemmery, L, Lambourne, V, Maltby, J, Vyas, S, Colley, J, Shinder, B, Singhal, S, Jones, J, Mills, M, Gleeson, D, Carnahan, M, Butterworth, J, Boulton, K, Taylor, N, George, K, Harding, T, Tregonning, J, Douglass, A, Brown, C, Clifford, G, Panter, S, Gocher, D, Shearman, J, Bray, G, Hamilton, M, Butcher, G, Forton, D, Mclindon, J, Curtis, J, Shewan, T, Cowan, M, Whatley, G, Nasseri, M, Grover, B, Sivaramakrishnan, N, Ducker, S, Houghton, K, Griffiths, L, Tripoli, S, Pitcher, M, Shpuza, E, White, N, Ghosh, D, Douds, A, Green, M, Brookes, M, Cumlat, L, Wong, V, Warner, K, Netherton, K, Mandal, A, Jain, S, Gupta, H, Sanghi, P, Pereira, S, Gunson, B, Lim, R, Gallagher, S, Clement, D, Brind, A, Watts, G, Mupudzi, M, Wright, M, Gitahi, J, Gordon, F, Unitt, E, Pateman, H, Batham, S, Delahooke, T, Grant, A, Conder, J, Higham, A, Cox, M, O'Donohoe, L, Currie, L, King, A, Oblak, M, Collins, C, Whalley, S, Quinn, M, Baird, Y, Amey, I, Fraser, J, Li, A, Cotterill, D, Bell, A, Singhal, A, Gee, I, Greer, S, Ang, Y, Ransford, R, Allison, J, Gotto, J, Dyer, S, Sweeting, H, Millson, C, Labbadia, G, Bragazzi, M, Andreone, P, Azzaroli, F, Galli, A, Tarocchi, M, Gasbarrini, A, Grieco, A, Marrone, G, Valenti, L, Maroni, L, Rigamonti, C, Picciotto, A, Sampaziotis, Fotios [0000-0003-0812-7586], Sandford, Richard [0000-0002-7437-0560], Apollo - University of Cambridge Repository, Carbone, Marco, Nardi, Alessandra, Flack, Steve, Carpino, Guido, Varvaropoulou, Nikoletta, Gavrila, Caiu, Spicer, Ann, Badrock, Jonathan, Bernuzzi, Francesca, Cardinale, Vincenzo, Ainsworth, Holly F, Heneghan, Michael A, Thorburn, Dougla, Bathgate, Andrew, Jones, Rebecca, Neuberger, James M, Battezzati, Pier Maria, Zuin, Massimo, Taylor-Robinson, Simon, Donato, Maria F, Kirby, John, Mitchell-Thain, Robert, Floreani, Annarosa, Sampaziotis, Fotio, Muratori, Luigi, Alvaro, Domenico, Marzioni, Marco, Miele, Luca, Marra, Fabio, Giannini, Edoardo, Gaudio, Eugenio, Ronca, Vincenzo, Bonato, Giulia, Cristoferi, Laura, Malinverno, Federica, Gerussi, Alessio, Stocken, Deborah D, Cordell, Heather J, Hirschfield, Gideon M, Alexander, Graeme J, Sandford, Richard N, Jones, David E, Invernizzi, Pietro, Mells, George F, Thomas, Caradog, Rahman, Meshbah, Yapp, Tom, Lye Ch'ng, Chin, Harrison, Melanie, Sturgess, Richard, Galaska, Roman, Healey, Chri, Whiteman, Jessica, Czaijkowski, Marek, Gray, Catherine, Gunasekera, Anton, Gyawli, Pranab, Premchand, Purushothaman, Mann, Steven, Elliott, Keith, Kapur, Kapil, Watson, Alan, Foster, Graham, Trembling, Paul, Subhani, Javaid, Harvey, Rory, McCorry, Roger, Adgey, Carolyn, Hobson, Lucie, Mulvaney-Jones, Caroline, Evans, Richard, Mathialahan, Thiriloganathan, Ramanaden, David, Gasem, Jaber, Van Duyvenvoorde, Greta, Shorrock, Christopher, Seward, Katie, Southern, Paul, Tibble, Jeremy, Penn, Ruth, Gorard, David, Maiden, Jane, Damant, Rose, Palegwala, Altaf, Jones, Susan, Alexander, Graeme, Mells, George, Sandford, Richard, Dolwani, Sunil, Prince, Martin, Silvestre, Valeria, Foxton, Matthew, Dungca, Eleanor, Mitchison, Harriet, Wheatley, Natalie, Gooding, Ian, Doyle, Helen, Karmo, Mazn, Kent, Melanie, Saksena, Sushma, Braim, Delyth, Patel, Minesh, Lord, Susan, Ede, Roland, Paton, Alison, Austin, Andrew, Lancaster, Nicola, Sayer, Joanna, Gibbins, Andrew, Hogben, Karen, Hovell, Chri, Fisher, Neil, Carter, Martyn, Koss, Konrad, Musselwhite, Janine, Muscariu, Florin, Piotreowicz, Andrzej, McKay, Alexandra, Grimley, Charle, Neal, David, Ting Tan, Lai, Lim, Guan, Brighton, Jacqueline, Foale, Carole, Ala, Aftab, Saeed, Athar, Flahive, Kerry, Wood, Gordon, Townshend, Paula, Ford, Chri, Brown, Jonathan, Kordula, Jean, Bowles, Jane, Wilkinson, Mark, Palmer, Caroline, Ramage, John, Gordon, Harriet, Featherstone, Jame, Ridpath, Jo, Ngatchu, Theodore, Levi, Sa, Shaukat, Syed, Sadeghian, Joy, Shidrawi, Ray, Williams, Bronwen, Abouda, George, Jones, Sarah, Duggan, Claire, Hynes, Abigail, Narain, Mark, Rees, Ian, Salam, Imroz, Crossey, Mary, Brown, Ashley, MacNicol, Carolyn, Williams, Simon, Wilhelmsen, Elva, Banim, Paul, Raymode, Parizade, Chilton, Andrew, Das, Debasish, Lee, Hye-Jeong, Curtis, Howard, Heneghan, Michael, Gess, Marku, Durant, Emma, Drake, I.M., Bishop, Rebecca, Davies, Mervyn, Aldersley, Mark, Ncube, Noma, McNair, Alistair, Srirajaskanthan, Raj, Sen, Sambit, Casey, Rebecca, Bird, George, Mendall, Mike, Cowley, Caroline, Barnardo, Adrian, Kitchen, Paul, Yoong, Kevin, Amore, Kelly, Sirdefield, Dawn, Orpe, Jacky, Mathew, Ray, MacFaul, George, Wrigth, Aruna, Shah, Amir, Evans, Chri, Keggans, Janie, Bird, Bridget, Baxter, Gwen, Saha, Subrata, Pollock, Katharine, Hughes, Maggie, Bramley, Peter, Grieve, Emma, Young, Karin, Fraser, Andrew, Mukhopadhya, Ashi, Ocker, Kate, Mills, Peter, Hines, Franci, Shallcross, Chri, Wilkins, Joy, Grellier, Leonie, Campbell, Stewart, Martin, Kirsty, Innes, Caron, Shepherd, Alan, Rushbrook, Simon, Valliani, Talal, Przemioslo, Robert, Fairlamb, Helen, Macdonald, Chri, Eastick, Anne, Metcalf, Jane, Tanqueray, Elizabeth, Shmueli, Udi, Holbrook, Becky, Davis, Andrew, Browning, Julie, Naqvi, Asifabba, Walker, Kirsten, Lee, Tom, Verheyden, Juliette, Slininger, Susan, Ryder, Stephen D, Chapman, Roger, Collier, Jane, O'Donnell, Denise, Stafford, Lizzie, Williamson, Kate, Kent, Linda, Klass, Howard, Ninkovic, Mary, March, Linda, Cramp, Matthew, Simpson, Diane, Dickson, Christine, Sharer, Nichola, Hayes, Maria, Goggin, Patrick, Quinne, Mary, Pearson, Sallyanne, Hoeroldt, Barbara, Jones, Linda, Wright, Alice, Booth, Jonathan, Loftus, Alison, Lipscomb, George, Dewhurst, Hannah, Gunter, Emma, Williams, Earl, Fouracres, Anna, Farrington, Liz, Graves, Lyn, Hussaini, Hyder, Stableforth, Bill, Marriott, Suzie, Ayres, Reuben, Leoni, Marina, Burroughs, Andrew, Marshall, Eileen, Tyrer, David, Martin, Kate, Lombard, Martin, Patanwala, Imran, Dali-Kemmery, Lola, Lambourne, Victoria, Maltby, Julia, Vyas, Samir, Colley, Julie, Shinder, Bal, Singhal, Saket, Jones, Jayne, Mills, Marisa, Gleeson, Dermot, Carnahan, Mandy, Butterworth, Jeff, Boulton, Kerenza, Taylor, Natalie, George, Keith, Harding, Tim, Tregonning, Julie, Douglass, Andrew, Brown, Carly, Clifford, Gayle, Panter, Simon, Gocher, Denise, Shearman, Jeremy, Bray, Gary, Hamilton, Maria, Butcher, Graham, Forton, Daniel, Mclindon, John, Curtis, Janette, Das, Debashi, Shewan, Tracey, Cowan, Matthew, Whatley, Gregory, Nasseri, Mariam, Grover, Bob, Sivaramakrishnan, Nurani, Ducker, Samantha, Houghton, Kathryn, Jones, David, Griffiths, Laura, Tripoli, Sherill, Pitcher, Maxton, Shpuza, Ervin, White, Nikki, Ghosh, Deb, Douds, Andrew, Green, Marie, Brookes, Matthew, Cumlat, Lourde, Wong, Voi Shim, Warner, Karen, Netherton, Kimberley, Mandal, Adtya, Jain, Snjiv, Gupta, Hemant, Sanghi, Pradeep, Pereira, Steve, Neuberger, Jame, Gunson, Bridget, Hirschfield, Gideon, Lim, Reina Teegan, Gallagher, Susan, Clement, Darren, Brind, Alison, Watts, Gill, Mupudzi, Mcdonald, Wright, Mark, Gitahi, Jane, Gordon, Fiona, Gocher, Deni, Unitt, Esther, Pateman, Hilary, Batham, Sally, Delahooke, Toby, Grant, Allister, Conder, Jill, Higham, Andrew, Cox, Mark, O'Donohoe, Lynn, Currie, Lynn, King, Alistair, Oblak, Metod, Collins, Carole, Whalley, Simon, Quinn, Marie, Baird, Yolanda, Amey, Isobel, Fraser, Jocelyn, Li, Andy, Cotterill, Donna, Bell, Andrew, Singhal, Amit, Gee, Ian, Greer, Sandra, Ang, Yeng, Ransford, Rupert, Allison, Joanna, Gotto, Jame, Dyer, Simon, Sweeting, Helen, Millson, Charle, Labbadia, Giancarlo, Bragazzi, Maria Consiglia, Andreone, Pietro, Azzaroli, Francesco, Galli, Andrea, Tarocchi, Mirko, Gasbarrini, Antonio, Grieco, Antonio, Marrone, Giuseppe, Donato, Maria Francesca, Valenti, Luca, Maroni, Luca, Rigamonti, Cristina, Picciotto, Antonino, and Medical Research Council (MRC)

Subjects
Male, Cholagogues and Choleretics, Cirrhosis, medicine.medical_treatment, PROGRESSION, Liver transplantation, PHENOTYPE, Gastroenterology, UDCA, 0302 clinical medicine, Primary biliary cirrhosis, Risk Factors, Medicine, Age of Onset, CIRRHOSIS, TREE, OUTCOMES, Settore MED/12 - Gastroenterologia, medicine.diagnostic_test, Liver Cirrhosis, Biliary, Ursodeoxycholic Acid, Area under the curve, URSODIOL, Middle Aged, Ursodeoxycholic acid, Treatment Outcome, Primary biliary cholangitis, ursodeoxycholic acid, 030220 oncology & carcinogenesis, Liver biopsy, Area Under Curve, 030211 gastroenterology & hepatology, Female, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, CONTROLLED-TRIAL, Hepatology, Decision Support Techniques, Time-to-Treatment, Biliary injury, 03 medical and health sciences, Internal medicine, Humans, Transaminases, Science & Technology, Gastroenterology & Hepatology, Italian PBC Study Group and the UK–PBC Consortium, business.industry, Bilirubin, medicine.disease, Alkaline Phosphatase, ROC Curve, CELLS, Linear Models, business
Abstract

Background: Treatment guidelines recommend a stepwise approach to primary biliary cholangitis: all patients begin treatment with ursodeoxycholic acid (UDCA) monotherapy and those with an inadequate biochemical response after 12 months are subsequently considered for second-line therapies. However, as a result, patients at the highest risk can wait the longest for effective treatment. We determined whether UDCA response can be accurately predicted using pretreatment clinical parameters. Methods: We did logistic regression analysis of pretreatment variables in a discovery cohort of patients in the UK with primary biliary cholangitis to derive the best-fitting model of UDCA response, defined as alkaline phosphatase less than 1·67 times the upper limit of normal (ULN), measured after 12 months of treatment with UDCA. We validated the model in an external cohort of patients with primary biliary cholangitis and treated with UDCA in Italy. Additionally, we assessed correlations between model predictions and key histological features, such as biliary injury and fibrosis, on liver biopsy samples. Findings: 2703 participants diagnosed with primary biliary cholangitis between Jan 1, 1998, and May 31, 2015, were included in the UK-PBC cohort for derivation of the model. The following pretreatment parameters were associated with lower probability of UDCA response: higher alkaline phosphatase concentration (p

Published
2018

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

Author

Cordell, Heather J., Younghun, Han, Mells, George F., Yafang, Li, Hirschfield, Gideon M., Greene, Casey S., Gang, Xie, Juran 7, Brian D., Dakai Zhu, 2, Qian 2, David C., Floyd, James A. B., Morley, Katherine I., Daniele Prati 11, Ana Lleo 12, Daniele, Cusi, Eric Gershwin 15, M., Anderson 8, Carl A., Lazaridis 7, Konstantinos N., Pietro, Invernizzi, Seldin 15, Michael F., Sandford, Richard N., Amos 2, Christopher I., Siminovitch, Katherine A., Schlicht 7, Erik M., Craig Lammert, 7, Atkinson 19, Elizabeth J., Chan 19, Landon L., Mariza de Andrade 19, Tobias Balschun 20, Mason 21, Andrew L., Myers 22, Robert P., Jinyi Zhang 23, Piotr Milkiewicz 24, Jia Qu 25, Odin 26, Joseph A., Luketic 27, Velimir A., Bacon 28, Bruce R., Bodenheimer Jr 29, Henry C., Valentina Liakina 30, Catherine Vincent 31, Cynthia Levy 32, Gregersen, Peter K., Almasio, 33 Piero L., 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, Lory Saveria Croce, ` 48, Andrea Crosignani 39, Maria Francesca Donato 46, Gianfranco Elia 49, Luca Fabris 50, Carlo Ferrari 49, Annarosa Floreani 51, Barbara Foglieni 11, Rosanna Fontana 37, Galli, Andrea, Roberta Lazzari 51, Fabio Macaluso 34, Federica Malinverno 46, Marra, Fabio, Marco Marzioni 40, Alberto Mattalia 54, Renzo Montanari 55, Lorenzo Morini 56, Filomena Morisco 57, Mousa Hani S., 41, Luigi Muratori 36, Paolo Muratori 36, Niro 37, Grazia A., Palmieri 58, Vincenzo O., 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 11, Mario, Strazzabosco, Sonia Tarallo 60, Tarocchi, Mirko, Claudio Tiribelli 48, Pierluigi Toniutto 64, Maria Vinci 65, Massimo, Zuin, Chin Lye Ch’ng, Mesbah Rahman 68, Tom Yapp 69, Richard Sturgess 70, Christopher Healey 71, Marek, Czajkowski, Anton, Gunasekera, 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, David, Gorard, Altaf Palegwala 98, Susan, Jones, Marco Carbone 101, Mohamed Dawwas 101, Graeme Alexander 101, Sunil, Dolwani, Martin Prince 104, Matthew Foxton 105, David Elphick 106, Harriet Mitchison 107, Ian Gooding 108, Mazn Karmo 109, Sushma, Saksena, Mike, Mendall, Minesh, Patel, Roland, Ede, Andrew Austin 119, Joanna, Sayer, Lorraine Hankey 122, Christopher Hovell 122, Neil Fisher 123, Martyn, Carter, Konrad Koss 126, Andrzej, Piotrowicz, Charles, Grimley, David, Neal, Guan Lim 135, Sass, Levi, Aftab Ala 138, Andrea Broad 139, Athar Saeed 139, Gordon Wood 140, Jonathan, Brown, Mark, Wilkinson, Harriet Gordon 145, John Ramage 146, Jo Ridpath 147, Theodore, Ngatchu, Bob Grover 151, Syed Shaukat 152, Ray Shidrawi 153, George, Abouda, Faiz Ali 156, Ian Rees 157, Imroz Salam 158, Mark Narain 159, Ashley, Brown, Simon Taylor Robinson 162, Simon Williams 163, Leonie Grellier 164, Paul Banim 165, Debasish Das 166, Andrew Chilton 166, Michael Heneghan 167, Howard, Curtis, Markus Gess 170, Ian, Drake, Mark, Aldersley, Mervyn, Davies, Rebecca, Jones, Alastair McNair 175, Raj Srirajaskanthan 176, Maxton, Pitcher, Sambit Sen 179, George, Bird, Adrian Barnardo 182, Paul Kitchen 182, Kevin Yoong 183, Oza, Chirag, Nurani Sivaramakrishnan 186, George MacFaul 187, David Jones 188, Amir Shah 189, Chris Evans 190, Subrata Saha 191, Katharine, Pollock, Peter, Bramley, Ashis, Mukhopadhya, Andrew, Fraser, Peter, Mills, Christopher, Shallcross, Stewart, Campbell, Andrew, Bathgate, Alan Shepherd 213, John Dillon 214, Simon Rushbrook 215, Robert Przemioslo 216 Christopher Macdonald, Jane, Metcalf, Udi Shmueli 221, Andrew, Davis, Asifabbas, Naqvi, Tom, Lee, Ryder, Stephen D., Jane Collier 231, Howard, Klass, Mary, Ninkovic, Matthew Cramp 238, Nicholas Sharer 239, Richard Aspinall 240, Patrick Goggin 240, Deb, Ghosh, 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 249, Steven, Mann, Martin Lombard 252, Paul Richardson 252, Imran Patanwala 252, Julia Maltby 253, Matthew Brookes 254, Ray, Mathew, Samir Vyas 257, Saket Singhal 258, Dermot, Gleeson, Sharat, Misra, Jeff, Butterworth, Keith George 265, Tim, Harding, Andrew, Douglass, Simon Panter 270, Jeremy Shearman 271, Gary Bray 272, Graham, Butcher, Daniel Forton 275, John, Mclindon, Matthew Cowan 279, Gregory Whatley 280, Aditya, Mandal, Hemant, Gupta, Pradeep, Sanghi, Sanjiv Jain 283, Steve Pereira 284, Geeta Prasad 285, Gill Watts 285, Mark Wright 286, James Neuberger 287, Fiona Gordon 288, Esther Unitt 289, Allister, Grant, Toby, Delahooke, Andrew Higham 293, Alison Brind 294, Mark Cox 295, Subramaniam Ramakrishnan 296, Alistair, King, Carole Collins 300, Simon, Whalley, Andy Li 303, Jocelyn Fraser 304, Andrew Bell 305, Voi Shim Wong 306, Amit, Singhal, Ian, Gee, Yeng Ang 312, Rupert Ransford 313, James Gotto 314, Charles, Millson, Jane Bowles 318, Caradog, Thomas, Melanie Harrison 70, Roman Galaska 71, Jennie, Kendall, Jessica, Whiteman, Caroline, Lawlor, Catherine, Gray, Keith Elliott 79, Caroline Mulvaney Jones, Lucie, Hobson, Greta Van Duyvenvoorde 90, Alison Loftus 91, Katie Seward 92, Ruth, Penn, Jane Maiden 98, Rose Damant 98, Janeane Hails 101, Rebecca, Cloudsdale, Valeria Silvestre 105, Sue Glenn 106, Eleanor Dungca 107, Natalie Wheatley 108, Helen Doyle 109, Melanie, Kent, Caroline, Hamilton, Delyth, Braim, Helen Wooldridge 117, Rachel Abrahams 117, Alison Paton 119, Nicola, Lancaster, Andrew Gibbins 122, Karen Hogben 122, Phillipa, Desousa, Florin, Muscariu, Janine, Musselwhite, Alexandra McKay 132, LaiTing Tan 135, Carole Foale 138, Jacqueline Brighton 138, Kerry Flahive 140, Estelle, Nambela, Paula, Townshend, Chris, Ford, Sophie, Holder, Caroline, Palmer, James Featherstone 147, Mariam Nasseri 151, Joy Sadeghian 153, Bronwen, Williams, Carol Thomas 156, Sally Ann Rolls 156, Abigail Hynes 159, Claire Duggan 159, Sarah Jones 159, Mary, Crossey, Glynis Stansfield 163, Carolyn MacNicol 163, Joy Wilkins 164, Elva Wilhelmsen 165, Parizade Raymode 166, Hye Jeong Lee 167, Emma, Durant, Rebecca, Bishop, Noma, Ncube, Sherill, Tripoli, Rebecca, Casey, Caroline Cowley 182, Richard Miller 183, Kathryn Houghton 188, Samantha Ducker 188, Fiona Wright 189, Bridget Bird 191, Gwen Baxter 191, Janie Keggans 191, Maggie, Hughes, Emma Grieve 196, Karin Young 196, Williams 197, D., Kate Ocker 199, Frances, Hines, Kirsty, Martin, Caron, Innes, Talal Valliani 216, Helen, Fairlamb, Sarah, Thornthwaite, Anne, Eastick, Elizabeth Tanqueray 221, Jennifer Morrison 222, Becky Holbrook 222, Julie, Browning, Kirsten, Walker, Susan, Congreave, Juliette, Verheyden, Susan, Slininger, Lizzie Stafford 231, Denise O’Donnell 231, Mark Ainsworth 231, Susan Lord 118, Linda, Kent, Linda March 238, Christine Dickson 239, Diane Simpson 239, Beverley Longhurst 240, Maria Hayes 240, Ervin, Shpuza, Nikki, White, Sarah, Besley, 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 254, Dawn, Sirdefield, Kelly Amor 255, Julie Colley 258, Bal Shinder 258, Jayne Jones 260, Marisa Mills 260, Mandy, Carnahan, Natalie Taylor 265, Kerenza Boulton 265, Julie, Tregonning, Carly Brown 270, Gayle Clifford 270, Emily Archer 271, Maria, Hamilton, Janette Curtis 278, Tracey Shewan 279, Sue Walsh 280, Karen, Warner, Kimberley Netherton 283, Mcdonald Mupudzi 286, Bridget Gunson 287, Jane Gitahi 288, Denise Gocher 289, Sally, Batham, Hilary, Pateman, Senayon, Desmennu, Jill Conder 293, Darren Clement 294, Susan Gallagher 294, Jacky Orpe 256, PuiChing Chan 296, Lynn, Currie, Lynn, O’Donohoe, 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 312, Katie, Spurdle, Joanna, Allison, Simon, Dyer, Helen, Sweeting, Jean, Kordula, 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., Seldin, M. F., Sandford, R. N., Amos, C. I., Siminovitch, K. A., Schlicht, E. M., Lammert, C., Atkinson, E. J., Chan, L. L., De Andrade, M., Balschun, T., Mason, A. L., Myers, R. P., Zhang, J., Milkiewicz, P., Qu, J., Odin, J. A., Luketic, V. A., Bacon, B. R., Bodenheimer, H. C., Liakina, V., Vincent, C., Levy, C., Gregersen, P. K., Almasio, P. L., Alvaro, D., Andreone, P., Andriulli, A., Barlassina, C., Battezzati, P. M., Benedetti, A., Bernuzzi, F., Bianchi, I., Bragazzi, M. C., Brunetto, M., Bruno, S., Casella, G., Coco, B., Colli, A., Colombo, M., Colombo, S., Cursaro, C., Croce, L. S., Crosignani, A., Donato, M. F., 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., Mousa Hani, S., Muratori, L., Muratori, P., Niro, G. A., Palmieri, V. O., 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., Zuin, M., Ch'Ng, C. L., Rahman, M., Yapp, T., Sturgess, R., Healey, C., Czajkowski, M., Gunasekera, A., Gyawali, P., Premchand, P., Kapur, K., Marley, R., Foster, G., Watson, A., Dias, A., Subhani, J., Harvey, R., Mccorry, R., Ramanaden, D., Gasem, J., Evans, R., Mathialahan, T., Shorrock, C., Lipscomb, G., Southern, P., Tibble, J., Gorard, D., Palegwala, A., Jones, S., Carbone, M., Dawwas, M., Alexander, G., Dolwani, S., Prince, M., Foxton, M., Elphick, D., Mitchison, H., Gooding, I., Karmo, M., Saksena, S., Mendall, M., Patel, M., Ede, R., Austin, A., Sayer, J., Hankey, L., Hovell, C., Fisher, N., Carter, M., Koss, K., Piotrowicz, A., Grimley, C., Neal, D., Lim, G., Levi, S., Ala, A., Broad, A., Saeed, A., Wood, G., Brown, J., Wilkinson, M., Gordon, H., Ramage, J., Ridpath, J., Ngatchu, T., Grover, B., Shaukat, S., Shidrawi, R., Abouda, G., Ali, F., Rees, I., Salam, I., Narain, M., Brown, A., Taylor-Robinson, S., Williams, S., Grellier, L., Banim, P., Das, D., Chilton, A., Heneghan, M., Curtis, H., Gess, M., Drake, I., Aldersley, M., Davies, M., Jones, R., Mcnair, A., Srirajaskanthan, R., Pitcher, M., Sen, S., Bird, G., Barnardo, A., Kitchen, P., Yoong, K., Chirag, O., Sivaramakrishnan, N., Macfaul, G., Jones, D., Shah, A., Evans, C., Saha, S., Pollock, K., Bramley, P., Mukhopadhya, A., Fraser, A., Mills, P., Shallcross, C., Campbell, S., Bathgate, A., Shepherd, A., Dillon, J., Rushbrook, S., Przemioslo, R., Macdonald, C., Metcalf, J., Shmueli, U., Davis, A., Naqvi, A., Lee, T., Stephen, D., Collier, J., Klass, H., Ninkovic, M., Cramp, M., Sharer, N., Aspinall, R., Goggin, P., Ghosh, D., Douds, A., Hoeroldt, B., Booth, J., Williams, E., Hussaini, H., Stableforth, W., Ayres, R., Thorburn, D., Marshall, E., Burroughs, A., Mann, S., Lombard, M., Richardson, P., Patanwala, I., Maltby, J., Brookes, M., Mathew, R., Vyas, S., Singhal, S., Gleeson, D., Misra, S., Butterworth, J., George, K., Harding, T., Douglass, A., Panter, S., Shearman, J., Bray, G., Butcher, G., Forton, D., Mclindon, J., Cowan, M., Whatley, G., Mandal, A., Gupta, H., Sanghi, P., Jain, S., Pereira, S., Prasad, G., Watts, G., Wright, M., Neuberger, J., Gordon, F., Unitt, E., Grant, A., Delahooke, T., Higham, A., Brind, A., Cox, M., Ramakrishnan, S., King, A., Collins, C., Whalley, S., Li, A., Fraser, J., Bell, A., Wong, V. S., Singhal, A., Gee, I., Ang, Y., Ransford, R., Gotto, J., Millson, C., Bowles, J., Thomas, C., Harrison, M., Galaska, R., Kendall, J., Whiteman, J., Lawlor, C., Gray, C., Elliott, K., Mulvaney-Jones, C., Hobson, L., Van Duyvenvoorde, G., Loftus, A., Seward, K., Penn, R., Maiden, J., Damant, R., Hails, J., Cloudsdale, R., Silvestre, V., Glenn, S., Dungca, E., Wheatley, N., Doyle, H., Kent, M., Hamilton, C., Braim, D., Wooldridge, H., Abrahams, R., Paton, A., Lancaster, N., Gibbins, A., Hogben, K., Desousa, P., Muscariu, F., Musselwhite, J., Mckay, A., Tan, L., Foale, C., Brighton, J., Flahive, K., Nambela, E., Townshend, P., Ford, C., Holder, S., Palmer, C., Featherstone, J., Nasseri, M., Sadeghian, J., Williams, B., Rolls, S. -A., Hynes, A., Duggan, C., Crossey, M., Stansfield, G., Macnicol, C., Wilkins, J., Wilhelmsen, E., Raymode, P., Lee, H. -J., Durant, E., Bishop, R., Ncube, N., Tripoli, S., Casey, R., Cowley, C., Miller, R., Houghton, K., Ducker, S., Wright, F., Bird, B., Baxter, G., Keggans, J., Hughes, M., Grieve, E., Young, K., Williams, D., Ocker, K., Hines, F., Martin, K., Innes, C., Valliani, T., Fairlamb, H., Thornthwaite, S., Eastick, A., Tanqueray, E., Morrison, J., Holbrook, B., Browning, J., Walker, K., Congreave, S., Verheyden, J., Slininger, S., Stafford, L., O'Donnell, D., Ainsworth, M., Lord, S., Kent, L., March, L., Dickson, C., Simpson, D., Longhurst, B., Hayes, M., Shpuza, E., White, N., Besley, S., Pearson, S., Wright, A., Jones, L., Gunter, E., Dewhurst, H., Fouracres, A., Farrington, L., Graves, L., Marriott, S., Leoni, M., Tyrer, D., Dali-Kemmery, L., Lambourne, V., Green, M., Sirdefield, D., Amor, K., Colley, J., Shinder, B., Jones, J., Mills, M., Carnahan, M., Taylor, N., Boulton, K., Tregonning, J., Brown, C., Clifford, G., Archer, E., Hamilton, M., Curtis, J., Shewan, T., Walsh, S., Warner, K., Netherton, K., Mupudzi, M., Gunson, B., Gitahi, J., Gocher, D., Batham, S., Pateman, H., Desmennu, S., Conder, J., Clement, D., Gallagher, S., Orpe, J., Chan, P., Currie, L., O'Donohoe, L., Oblak, M., Morgan, L., Quinn, M., Amey, I., Baird, Y., Cotterill, D., Cumlat, L., Winter, L., Greer, S., Spurdle, K., Allison, J., Dyer, S., Sweeting, H., Kordula, J., 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, Gershwin, M. Eric, Anderson, Carl A., Lazaridis, Konstantinos N., Invernizzi, Pietro, Seldin, Michael F., Sandford, Richard N., Amos, Christopher I., Siminovitch, Katherine A., Schlicht, Erik M., Lammert, Craig, Atkinson, Elizabeth J., Chan, Landon L., De Andrade, Mariza, Balschun, Tobia, Mason, Andrew L., Myers, Robert P., Zhang, Jinyi, Milkiewicz, Piotr, Qu, Jia, Odin, Joseph A., Luketic, Velimir A., Bacon, Bruce R., Bodenheimer, Henry C., Liakina, Valentina, Vincent, Catherine, Levy, Cynthia, Gregersen, Peter K., 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, 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, 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, Charle, Neal, David, Lim, Guan, Levi, Sa, 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, Debasish, Chilton, Andrew, Heneghan, Michael, Curtis, Howard, Gess, Marku, 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, Chri, Saha, Subrata, Pollock, Katharine, Bramley, Peter, Mukhopadhya, Ashi, 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, Asifabba, Lee, Tom, Stephen, Dyder, Collier, Jane, Klass, Howard, Ninkovic, Mary, Cramp, Matthew, Sharer, Nichola, Aspinall, Richard, Goggin, Patrick, Ghosh, Deb, Douds, Andrew, Hoeroldt, Barbara, Booth, Jonathan, Williams, Earl, Hussaini, Hyder, Stableforth, William, Ayres, Reuben, Thorburn, Dougla, 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, Jame, 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, Jame, Millson, Charle, 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, 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Amey, I, Baird, Y, Cotterill, D, Cumlat, L, Winter, L, Greer, S, Spurdle, K, Allison, J, Dyer, S, Sweeting, H, and Kordula, J

Subjects
Liver Cirrhosis, Genetics and Molecular Biology (all), pathogenesi, risk assessment EMTREE medical terms: Article, genetic association, genotype, EMTREE drug terms: chemokine receptor CCR6, genetic risk, Biochemistry, meta-analysi, primary biliary cirrhosi, chemokine receptor CCR6 [EMTREE drug terms], single nucleotide polymorphism, genetic variability, Article [risk assessment EMTREE medical terms], Liver Cirrhosis, Biliary, pathogenesis, Biliary, Chemistry (all), STAT protein GEOBASE Subject Index: disease treatment, cohort analysis, genome wide meta analysis PBC, signal transduction, gene locus, cohort analysi, CBP, Article, Physics and Astronomy (all), macrophage inflammatory protein 3alpha, Humans, controlled study, human, interleukin 27, genome, Biochemistry, Genetics and Molecular Biology (all), meta analysi, interleukin 12p40, interleukin 12, Janus kinase, meta-analysis, pathogen, genetic predisposition, major clinical study, meta analysis, primary biliary cirrhosis, disease treatment [STAT protein GEOBASE Subject Index], Genome-Wide Association Study, gene locu
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, Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

Published
2015

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