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1. Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581]

Author

Heather J. Cordell, James J. Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D. Juran, Elizabeth J. Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A.R. Ferreira, Dylan Sun, David E. Jones, Steven Flack, Ann Spicer, Victoria L. Mulcahy, Jinyoung Byun, Younghun Han, Richard N. Sandford, Konstantinos N. Lazaridis, Christopher I. Amos, Gideon M. Hirschfield, Michael F. Seldin, Pietro Invernizzi, Katherine A. Siminovitch, Xiong Ma, Minoru Nakamura, George F. Mells, Andrew Mason, Catherine Vincent, Gang Xie, Jinyi Zhang, Andrea Affronti, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Francesco Azzaroli, Pier Maria Battezzati, Antonio Benedetti, Maria Consiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Vincenza Calvaruso, Vincenzo Cardinale, Giovanni Casella, Nora Cazzagon, Antonio Ciaccio, Barbara Coco, Agostino Colli, Guido Colloredo, Massimo Colombo, Silvia Colombo, Laura Cristoferi, Carmela Cursaro, Lory Saveria Crocè, Andrea Crosignani, Daphne D’Amato, Francesca Donato, Gianfranco Elia, Luca Fabris, Stefano Fagiuoli, Carlo Ferrari, Annarosa Floreani, Andrea Galli, Edoardo Giannini, Ignazio Grattagliano, Pietro Lampertico, Ana Lleo, Federica Malinverno, Clara Mancuso, Fabio Marra, Marco Marzioni, Sara Massironi, Alberto Mattalia, Luca Miele, Chiara Milani, Lorenzo Morini, Filomena Morisco, Luigi Muratori, Paolo Muratori, Grazia A. Niro, Sarah O’Donnell, Antonio Picciotto, Piero Portincasa, Cristina Rigamonti, Vincenzo Ronca, Floriano Rosina, Giancarlo Spinzi, Mario Strazzabosco, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Luca Valenti, Maria Vinci, Massimo Zuin, Hitomi Nakamura, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Hiromi Ishibashi, Masahiro Ito, Kiyoshi Migita, Hiromasa Ohira, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ota, Takuya Komura, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Keisuke Ario, Makoto Nakamuta, Tsutomu Yamashita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Seiji Tsunematsu, Iwao Yabuuchi, Yusuke Shimada, Kazuhiko Yamauchi, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Satoru Tsuruta, Hiroshi Kamitsukasa, Takeaki Sato, Naohiko Masaki, Tatsuro Kobata, Nobuyoshi Fukushima, Yukio Ohara, Toyokichi Muro, Eiichi Takesaki, Hitoshi Takaki, Tetsuo Yamamoto, Michio Kato, Yuko Nagaoki, Shigeki Hayashi, Jinya Ishida, Yukio Watanabe, Masakazu Kobayashi, Michiaki Koga, Takeo Saoshiro, Michiyasu Yagura, Keisuke Hirata, Atsushu Tanaka, Hajime Takikawa, Mikio Zeniya, Masanori Abe, Morikazu Onji, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Satoshi Yamagiwa, Masataka Seike, Koichi Honda, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Kentaro Kikuchi, Hirotoshi Ebinuma, Takashi Himoto, Michio Yasunami, Kazumoto Murata, Masashi Mizokami, Kazuhito Kawata, Shinji Shimoda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto, Katsuji Hirano, Takafumi Ichida, Akio Ido, Hirohito Tsubouchi, Kazuaki Chayama, Kenichi Harada, Yasuni Nakanuma, Yoshihiko Maehara, Akinobu Taketomi, Ken Shirabe, Yuji Soejima, Akira Mori, Shintaro Yagi, Shinji Uemoto, Egawa H, Tomohiro Tanaka, Noriyo Yamashiki, Sumito Tamura, Yasuhiro Sugawara, Norihiro Kokudo, Naga Chalasani, Vel Luketic, Joseph Odin, Kapil Chopra, Goncalo Abecasis, Michael Cantor, Giovanni Coppola, Aris Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Leland Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Evan K. Maxwell, William Salerno, Jeffrey C. Staples, Marcus B. Jones, Lyndon J. Mitnaul, Richard Sturgess, Christopher Healey, Andrew Yeoman, Anton V.J. Gunasekera, Paul Kooner, Kapil Kapur, V. Sathyanarayana, Yiannis Kallis, Javaid Subhani, Rory Harvey, Roger McCorry, Paul Rooney, David Ramanaden, Richard Evans, Thiriloganathan Mathialahan, Jaber Gasem, Christopher Shorrock, Mahesh Bhalme, Paul Southern, Jeremy A. Tibble, David A. Gorard, Susan Jones, George Mells, Victoria Mulcahy, Brijesh Srivastava, Matthew R. Foxton, Carole E. Collins, David Elphick, Mazn Karmo, Francisco Porras-Perez, Michael Mendall, Tom Yapp, Minesh Patel, Roland Ede, Joanne Sayer, James Jupp, Neil Fisher, Martyn J. Carter, Konrad Koss, Jayshri Shah, Andrzej Piotrowicz, Glyn Scott, Charles Grimley, Ian R. Gooding, Simon Williams, Judith Tidbury, Guan Lim, Kuldeep Cheent, Sass Levi, Dina Mansour, Matilda Beckley, Coral Hollywood, Terry Wong, Richard Marley, John Ramage, Harriet M. Gordon, Jo Ridpath, Theodore Ngatchu, Vijay Paul Bob Grover, Ray G. Shidrawi, George Abouda, L. Corless, Mark Narain, Ian Rees, Ashley Brown, Simon Taylor-Robinson, Joy Wilkins, Leonie Grellier, Paul Banim, Debasish Das, Michael A. Heneghan, Howard Curtis, Helen C. Matthews, Faiyaz Mohammed, Mark Aldersley, Raj Srirajaskanthan, Giles Walker, Alistair McNair, Amar Sharif, Sambit Sen, George Bird, Martin I. Prince, Geeta Prasad, Paul Kitchen, Adrian Barnardo, Chirag Oza, Nurani N. Sivaramakrishnan, Prakash Gupta, Amir Shah, Chris D.J. Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Stephen T. Barclay, Natasha McDonald, Andrew J. Bathgate, Kelvin Palmer, John F. Dillon, Simon M. Rushbrook, Robert Przemioslo, Chris McDonald, Andrew Millar, Cheh Tai, Stephen Mitchell, Jane Metcalf, Syed Shaukat, Mary Ninkovic, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom J.W. Lee, Stephen Ryder, Jane Collier, Howard Klass, Matthew E. Cramp, Nichols Sharer, Richard Aspinall, Deb Ghosh, Andrew C. Douds, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Steven Mann, Douglas Thorburn, Aileen Marshall, Imran Patanwala, Aftab Ala, Julia Maltby, Ray Matthew, Chris Corbett, Sam Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Harriet Mitchison, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Graham Butcher, Daniel Forton, Zahid Mahmood, Matthew Cowan, Debashis Das, Chin Lye Ch'ng, Mesbah Rahman, Gregory C.A. Whatley, Emma Wesley, Aditya Mandal, Sanjiv Jain, Stephen P. Pereira, Mark Wright, Palak Trivedi, Fiona H. Gordon, Esther Unitt, Altaf Palejwala, Andrew Austin, Vishwaraj Vemala, Allister Grant, Andrew D. Higham, Alison Brind, Ray Mathew, Mark Cox, Subramaniam Ramakrishnan, Alistair King, Simon Whalley, Jocelyn Fraser, S.J. Thomson, Andrew Bell, Voi Shim Wong, Richard Kia, Ian Gee, Richard Keld, Rupert Ransford, James Gotto, and Charles Millson

Subjects
Science & Technology, Hepatology, Gastroenterology & Hepatology, Italian PBC Study Group, Japan-PBC-GWAS Consortium, UK-PBC Consortium, Chinese PBC Consortium, 1103 Clinical Sciences, US PBC Consortium, Canadian PBC Consortium, Life Sciences & Biomedicine, PBC Consortia, 1117 Public Health and Health Services
Published
2021

2. Challenges and opportunities of COVID-19 for gastroenterology and hepatology services

Author

Andrew C Douds, Rupert Ransford, and Tony C.K. Tham

Subjects
medicine.medical_specialty, Hepatology, Coronavirus disease 2019 (COVID-19), business.industry, Public health, Gastroenterology, Ethnic group, health service research, clinical decision making, liver, Mental health, 03 medical and health sciences, 0302 clinical medicine, Work (electrical), Nursing, Health care, Pandemic, medicine, 030211 gastroenterology & hepatology, 030212 general & internal medicine, endoscopy, business, Professional Matters, Recovery phase
Abstract

We are all aware that the COVID-19 pandemic has had the most profound impact on society and healthcare in our lifetime. As we are now in the recovery phase of the pandemic, we have an opportunity to reboot and redesign our services including the way we work for the benefit of the patient.1 We will consider the challenges and opportunities for healthcare staff and services. Many of our healthcare colleagues are also patients with chronic diseases and have raised concerns about time away from work because of shielding, effect on their mental health, uncertainty about whom to talk to about their condition and confusion about receiving conflicting advice.2 Time off work has also adversely impacted on rotas and teams. Healthcare workers from a black, Asian and minority ethnic background (BAME) are also rightly worried about their own risks from COVID-19 as evidence shows that they are more disproportionately affected with more severe disease.3 Public Health England has recommended that BAME healthcare workers should be risk assessed by their employers followed by any necessary precautions.4 Even before the COVID-19 pandemic, it was recognised that the well-being of healthcare professionals is an important factor in the provision of good service5 and the stress of the pandemic has brought mental as well as physical health into sharp focus. Many gastroenterologists want to change the way they work and redesigning services provides an opportunity to improve work–life balance in addition to the quality of care for patients. Many of our colleagues during the pandemic have seen the benefits of working from home during hours that suit them and would like to continue working flexibly. This has been adversely affected by the COVID-19 pandemic with 66% of trainees not undertaking clinics and 53% feel that they are unlikely to achieve …

Published
2020
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3. Delay in Transit: selected recommendations from the NCEPOD report on acute bowel obstruction

Author

Alison Culkin, Martin Sinclair, Hannah Shotton, Andrew C. Douds, and Antony Michalski

Subjects
medicine.medical_specialty, Hepatology, Operating theatres, business.industry, Gastroenterology, 030208 emergency & critical care medicine, Delayed treatment, 030230 surgery, medicine.disease, Bowel obstruction, 03 medical and health sciences, 0302 clinical medicine, Clinical pathway, Increased risk, Emergency medicine, Medicine, Stage (cooking), business, Hospital stay, Small Bowel and Nutrition
Abstract

Delayed in Transit, the report of the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) on acute bowel obstruction (ABO), highlighted a number of areas for improvement in this group of patients. The overarching finding was that there were delays in the pathway of care for patients with ABO at every stage of the clinical pathway, including diagnosis, decision-making and the availability of operating theatres. Furthermore, basic measures including hydration, nutritional screening and nutritional assessment were noted to be deficient. Patients who were admitted to non-surgical wards had an increased risk of delayed treatment and subsequently a longer starvation period. There was room for improvement of nutritional screening and assessment on admission, throughout the hospital stay and on discharge. A selection of the report recommendations that address these areas requiring improvement is discussed here.

Published
2021

4. X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis

Author

S. Abiru, John F. Dillon, Yasuhiro Miyake, Piero Portincasa, Giancarlo Spinzi, R. Harvey, T. Ngatchu, Agostino Colli, M. Taniai, K. Flahive, Masanori Abe, B. Hoeroldt, S. Holder, Howard Curtis, María Isabel Colombo, C. MacNicol, Gang Xie, Andrew Chilton, H. Hussaini, Cristina Rigamonti, M. Kato, Shintaro Yagi, G. Abouda, D. Tyrer, Chris D. Evans, Christopher I. Amos, K. Koss, Kazuaki Chayama, P. Premchand, K. Migita, Simon Panter, Marco Marzioni, Silvia Colombo, Konstantinos N. Lazaridis, M. Yagura, Ashley Brown, D. Gocher, Domenico Alvaro, K. Murata, Mark Wright, Piero Luigi Almasio, C. Healey, A. Ciaccio, N. Wheatley, Vincenzo Cardinale, T. Delahooke, Chiara Milani, T. Shewan, W. Stableforth, S. Levi, Mark L. Green, James V. Jones, Y. Baird, Aftab Ala, Burroughs Ak, D. Williams, K. Ario, P. Sanghi, Hemant Gupta, P. Southern, L. Farrington, M. Hamilton, Andrew D. Higham, I. Yabuuchi, H. Yatsuhashi, Lorenzo Morini, T. Yamamoto, Douglas Thorburn, M. Carnahan, N. Nishida, Susan Slininger, M. Koga, K. Honda, Annarosa Floreani, Andrew Douglass, K. Netherton, M. Yasunami, Hirohito Tsubouchi, F. Donato, K. Walker, U. Shmueli, Paolo Muratori, Ray Mathew, J. Maiden, E. Dungca, Subramaniam Ramakrishnan, S. Vyas, Helen Sweeting, Subrata Saha, T. Komeda, T. Komatsu, H. J. Lee, Maria Consiglia Bragazzi, T. Komura, C. Thomas, C. Shallcross, C. Duggan, J. Kordula, F. Muscariu, Lourdes Cumlat, Imran Patanwala, Giulia Cardamone, L. Morgan, J. Brighton, Masao Honda, H. Nakamura, David Jones, Raj Srirajaskanthan, M. E. Gershwin, T. Muro, L. Stafford, N. Fukushima, Graham P. Butcher, Andrea Crosignani, George Lipscomb, K. Hirata, Y. Nagaoki, S. Mann, Paul G. Richardson, David A Elphick, M. Mupudzi, Y. Ohara, E. Grieve, Gayle Clifford, Claudio Tiribelli, M. Quinn, G. Van Duyvenvoorde, E. Archer, Tatsuki Ichikawa, J. Maltby, T. Arinaga-Hino, Simon Williams, A. King, Yasuni Nakanuma, H. Doyle, A. Brind, Nora Cazzagon, H. Ota, Daphne D’Amato, K. Hogben, H. Wooldridge, J. Wilkins, Shuichi Kaneko, L. Hankey, Gordon Wood, Andrew Fraser, K. Martin, A. Naqvi, M. Ninkovic, M. Patel, Yoshihiko Maehara, Kapil Kapur, I. Amey, Vincenza Calvaruso, Kenichi Harada, T. Yamashita, James Neuberger, N. Taylor, T. Lee, J. Featherstone, C. Lawlor, K. Seward, Satoshi Yamagiwa, Andrea Galli, L. Tan, Kentaro Kikuchi, K. Furuta, Mark A. Ainsworth, Hiromasa Ohira, Esther Unitt, Yosuke Kawai, N. Lancaster, D. Simpson, R. Shidrawi, I. Salam, A.J. Bell, Pietro Andreone, J. Ishida, Voi Shim Wong, N Fisher, Andrew C. Douds, R. Penn, Matthew Foxton, A. Watson, Andrew Mason, S. Walsh, Hiromi Ishibashi, Daniel M. Forton, Giovanni Casella, H. Takaki, K. Yamauchi, Pietro Lampertico, Osamu Yokosuka, M. Koda, M. Davies, H. Mitchison, P. Gyawali, G. Bird, M. Hughes, L. Jones, C. Hamilton, A. Hynes, R. Galaska, Fabio Marra, Debasish Das, C. Cowley, A. Fouracres, Yasuhiko Sugawara, E. Mita, T. Saoshiro, Akinobu Taketomi, Robert P. Myers, R. Przemioslo, F. Wright, L. Hobson, L. Currie, J. Allison, J. Hails, Noriyo Yamashiki, Massimo Zuin, C. Grimley, Alessio Gerussi, S. Besley, Stefano Duga, A. Piotrowicz, H. Kouno, L. Dali-kemmery, H. Sakai, M. Mizokami, Stefano Fagiuoli, Amy Davis, Pier Maria Battezzati, Masao Nagasaki, Luigi Muratori, A. Mori, S. Desmennu, S. Jones, R. Abrahams, Keith George, F. Makita, J. Brown, D. Gorard, Satoru Joshita, M. Mills, Pierluigi Toniutto, S. Campbell, J. Butterworth, S. Dyer, Filomena Morisco, Norihiro Kokudo, T. Yapp, C. Shorrock, Floriano Rosina, E. Walker, Shinji Uemoto, H. Takahashi, Simon M. Rushbrook, K. Amor, E. Marshall, J. Browning, S. Batham, Luca Fabris, Paul R. Banim, Meenakshi Narain, M. Harada, Dermot Gleeson, N. Hirashima, M. Kikuchi, T. Nikami, Gideon M. Hirschfield, Carlo Ferrari, G. Prasad, O. Chirag, Katsushi Tokunaga, M. Nasseri, Rosanna Asselta, Y. Lu, Ken Shirabe, D. Sirdefield, George F. Mells, K. Sugi, R. Ayres, G. Whatley, A. Singhal, M. Leoni, N. Sivaramakrishnan, T. Harding, Rupert Ransford, Anton V J Gunasekera, C. Mulvaney-Jones, D. Ramanaden, M. Mendall, Muhammad F. Dawwas, Dave Jones, Luca Valenti, Earl J. Williams, Markus Gess, Peter Bramley, A. McNair, E. Hashimoto, P. Townshend, C. Ford, Mario Strazzabosco, Luca Miele, Matthew J Brookes, J. Colley, Mark Wilkinson, H. Dewhurst, Charles Millson, E. Shpuza, Shinji Shimoda, T. Himoto, P. Kitchen, M. Nakamuta, Hiroaki Nishimura, Martin Lombard, Kevork M. Peltekian, M. Pitcher, G. Lim, L. Graves, C. Palmer, S. Lord, S. Katsushima, S. Tripoli, Andrew Austin, N. White, B. Grover, S. Congreave, M. Prince, Rebecca Jones, K. Hirano, A. Shepherd, Y. Mano, Michael A. Heneghan, Richard Sandford, L. O'Donohoe, Marco Carbone, S. A. Rolls, Patrick Goggin, M. L. Cowan, M. Crossey, A. Loftus, K. Young, Mesbah Rahman, Cameron N. Ghent, E. Nambela, M. Xiong, L. Grellier, Sunil Dolwani, Antonio Picciotto, Gill Watts, Alberto Mattalia, Elvezia Maria Paraboschi, J. Orpe, Takeji Umemura, Yuki Hitomi, Fiona H. Gordon, Shotaro Sakisaka, A. Dias, Chin Lye Ch'ng, M. Carter, A. Mandal, Yufang Shi, Takafumi Ichida, N. Masaki, M. Oblak, S. Nagaoka, Kevin Yoong, O. Gervais, Minoru Nakamura, Kazuhiko Nakao, S. Taylor-Robinson, L. Kent, Sushma Saksena, A. Affronti, K. Boulton, R. Ede, H. Pateman, K. Yoshizawa, G. Bray, H. Ebinuma, Yeng Ang, Akio Ido, John Ramage, Richard Sturgess, C. Gray, E. Durant, M. Hayes, A. Saeed, J. Keggans, J. Gitahi, T. Valliani, Edoardo G. Giannini, C. Foale, A. Palegwala, Lory Saveria Crocè, K. Matsushita, S. Shaukat, J. Mclindon, S. Pearson, A. Barnardo, A. Wright, Mirko Tarocchi, R Marley, M. Kent, C. Dickson, A. Gibbins, J. Whiteman, S. Singhal, Richard Aspinall, M. Ito, Laura Cristoferi, Maurizia Rossana Brunetto, J. Booth, A. Bathgate, Morikazu Onji, A. Grant, A. Paton, Y. Aiba, P. Chan, J. Sayer, S. Whalley, T. Mathialahan, J. Gotto, T. Kanda, B. Williams, K. Elliott, P. Raymode, Akinobu Takaki, V. Silvestre, I. Gee, C. Hovell, Graham R. Foster, D. Cotterill, G. Stansfield, Grazia Anna Niro, J. Conder, Yoshiyuki Ueno, A. Shah, Jane Metcalf, S. Hayashi, T. Sato, S. Jain, J. Subhani, Donatella Barisani, A. McKay, Kuniaki Arai, Jeremy Shearman, Torao Tanaka, S. Glenn, S. E. O'Donnell, Federica Malinverno, Denise O'Donnell, R. Casey, N. Sharer, J. Bowles, J. Kendall, Maria Cristina Vinci, Antonio Benedetti, George MacFaul, K. Houghton, Vincenzo Ronca, P. Desousa, B. Holbrook, F. Ali, B. Longhurst, Atsushi Tanaka, Marek Czajkowski, R. Tang, Kazuhide Yamamoto, Y. Watanabe, Graeme J.M. Alexander, R. Cloudsdale, F. Hines, M. Karmo, Brian D. Juran, I. Gooding, Y. Takeyama, J. Fraser, A. Mukhopadhya, Sumihito Tamura, Hajime Takikawa, R. Damant, E. Wilhelmsen, M. Kobayashi, J. Tregonning, V. Lambourne, D. Clement, D. Braim, M. Shimada, S. Sen, Shaun Greer, C. Innes, E. Gunter, C. Brown, H. Klass, A. Komori, Andy Li, H. Fairlamb, N. Ncube, Yoshinori Shimada, M. Harrison, S. Marriott, I. Grattagliano, Savino Bruno, A. Naganuma, Xiangjun Gu, Michael F. Seldin, S. Thornthwaite, Peter R. Mills, Katherine A. Siminovitch, X. Liu, Masataka Seike, J. Curtis, Carmela Cursaro, Z. Li, Mikio Zeniya, K. Warner, B. Bird, Jane Collier, Bridget Gunson, S. Tsuruta, E. Tanqueray, Richard Evans, H. Kamitsukasa, R. Sugimoto, Jeremy Tibble, D. Neal, S. Ducker, Francesco Azzaroli, K. Spurdle, K. Ocker, M. Senju, C. Collins, Y. Nakamura, Matthew E. Cramp, Yuji Soejima, I. Drake, K. Ueno, T. Mannami, Clara Mancuso, M. Kawashima, M. Cox, S. S. Kohn, H. Shibata, Stephen D. Ryder, Christopher Macdonald, J. Ridpath, Stephen P. Pereira, L. March, Barbara Coco, J. Morrison, A. Broad, J. Verheyden, Angelo Andriulli, N. Higuchi, J. Musselwhite, R. Bishop, Gwen Baxter, Richard A. Miller, Guido Colloredo, A. Eastick, I. Rees, Deb Ghosh, L. Winter, Sara Massironi, R. McCorry, Gianfranco Elia, T. Kobata, N. Naeshiro, K. Pollock, J. Gasem, S. Gallagher, K. Jing, S. Misra, B. Shinder, Harriet Gordon, E. Takesaki, J. Sadeghian, S. Tsunematsu, Ana Lleo, M. Aldersley, Elizabeth J. Atkinson, Pietro Invernizzi, Heather J. Cordell, Asselta, R., Paraboschi, E. M., Gerussi, A., Cordell, H. J., Mells, G. F., Sandford, R. N., Jones, D. E., Nakamura, M., Ueno, K., Hitomi, Y., Kawashima, M., Nishida, N., Tokunaga, K., Nagasaki, M., Tanaka, A., Tang, R., Li, Z., Shi, Y., Liu, X., Xiong, M., Hirschfield, G., Siminovitch, K. A., Walker, E., Xie, G., Mason, A., Myers, R., Peltekian, K., Ghent, C., Atkinson, E., Juran, B., Lazaridis, K., Lu, Y., Gu, X., Jing, K., Amos, C., Affronti, A., Brunetto, M., Coco, B., Spinzi, G., Elia, G., Ferrari, C., Lleo, A., Muratori, L., Muratori, P., Portincasa, P., Colli, A., Bruno, S., Colloredo, G., Azzaroli, F., Andreone, P., Bragazzi, M., Alvaro, D., Cardinale, V., Cazzagon, N., Rigamonti, C., Floreani, A., Rosina, F., Ciaccio, A., Cristoferi, L., D'Amato, D., Malinverno, F., Mancuso, C., Massironi, S., Milani, C., O'Donnell, S. E., Ronca, V., Barisani, D., Lampertico, P., Donato, F., Fagiuoli, S., Almasio, P. L., Giannini, E., Cursaro, C., Colombo, M., Valenti, L., Miele, L., Andriulli, A., Niro, G. A., Grattagliano, I., Morini, L., Casella, G., Vinci, M., Battezzati, P. M., Crosignani, A., Zuin, M., Mattalia, A., Calvaruso, V., Colombo, S., Benedetti, A., Marzioni, M., Galli, A., Marra, F., Tarocchi, M., Picciotto, A., Morisco, F., Fabris, L., Croce, L. S., Tiribelli, C., Toniutto, P., Strazzabosco, 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., 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., Ryder, S. 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E., Seldin, M. F., Invernizzi, P., Asselta R., Paraboschi E.M., Gerussi A., Cordell H.J., Mells G.F., Sandford R.N., Jones D.E., Nakamura M., Ueno K., Hitomi Y., Kawashima M., Nishida N., Tokunaga K., Nagasaki M., Tanaka A., Tang R., Li Z., Shi Y., Liu X., Xiong M., Hirschfield G., Siminovitch K.A., Walker E., Xie G., Mason A., Myers R., Peltekian K., Ghent C., Atkinson E., Juran B., Lazaridis K., Lu Y., Gu X., Jing K., Amos C., Affronti A., Brunetto M., Coco B., Spinzi G., Elia G., Ferrari C., Lleo A., Muratori L., Muratori P., Portincasa P., Colli A., Bruno S., Colloredo G., Azzaroli F., Andreone P., Bragazzi M., Alvaro D., Cardinale V., Cazzagon N., Rigamonti C., Floreani A., Rosina F., Ciaccio A., Cristoferi L., D'Amato D., Malinverno F., Mancuso C., Massironi S., Milani C., O'Donnell S.E., Ronca V., Barisani D., Lampertico P., Donato F., Fagiuoli S., Almasio P.L., Giannini E., Cursaro C., Colombo M., Valenti L., Miele L., Andriulli A., Niro G.A., Grattagliano I., Morini L., Casella G., Vinci M., Battezzati P.M., Crosignani A., Zuin M., Mattalia A., Calvaruso V., Colombo S., Benedetti A., Marzioni M., Galli A., Marra F., Tarocchi M., Picciotto A., Morisco F., Fabris L., Croce L.S., Tiribelli C., Toniutto P., Strazzabosco 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., 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., Ryder S.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 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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., Aiba Y., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Kawai Y., Kohn S.-S., Gervais O., Migita K., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Higuchi N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Takikawa H., Ohira H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Carbone M., Cardamone G., Duga S., Gershwin M.E., Seldin M.F., Invernizzi P., Asselta, R, Paraboschi, E, Gerussi, A, Cordell, H, Mells, G, Sandford, R, Jones, D, Nakamura, M, Ueno, K, Hitomi, Y, Kawashima, M, Nishida, N, Tokunaga, K, Nagasaki, M, Tanaka, A, Tang, R, Li, Z, Shi, Y, Liu, X, Xiong, M, Hirschfield, G, Siminovitch, K, Walker, E, Xie, G, Mason, A, Myers, R, Peltekian, K, Ghent, C, Atkinson, E, Juran, B, Lazaridis, K, Lu, Y, Gu, X, Jing, K, Amos, C, Affronti, A, Brunetto, M, Coco, B, Spinzi, G, Elia, G, Ferrari, C, Lleo, A, Muratori, L, Muratori, P, Portincasa, P, Colli, A, Bruno, S, Colloredo, G, Azzaroli, F, Andreone, P, Bragazzi, M, Alvaro, D, Cardinale, V, Cazzagon, N, Rigamonti, C, Floreani, A, Rosina, F, Ciaccio, A, Cristoferi, L, D'Amato, D, Malinverno, F, Mancuso, C, Massironi, S, Milani, C, O'Donnell, S, Ronca, V, Barisani, D, Lampertico, P, Donato, F, Fagiuoli, S, Almasio, P, Giannini, E, Cursaro, C, Colombo, M, Valenti, L, Miele, L, Andriulli, A, Niro, G, Grattagliano, I, Morini, L, Casella, G, Vinci, M, Battezzati, P, Crosignani, A, Zuin, M, Mattalia, A, Calvaruso, V, Colombo, S, Benedetti, A, Marzioni, M, Galli, A, Marra, F, Tarocchi, M, Picciotto, A, Morisco, F, Fabris, L, Croce, L, Tiribelli, C, Toniutto, P, Strazzabosco, M, Ch'Ng, C, 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, 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, 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, Ryder, S, 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, 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, Hynes, A, Duggan, C, Crossey, M, Stansfield, G, Macnicol, C, Wilkins, J, Wilhelmsen, E, Raymode, P, Lee, H, 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, Aiba, Y, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Kawai, Y, Kohn, S, Gervais, O, Migita, K, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Higuchi, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Takikawa, H, Ohira, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Carbone, M, Cardamone, G, Duga, S, Gershwin, M, Seldin, M, Invernizzi, P, Asselta R, Paraboschi EM, Gerussi A, Cordell HJ, Mells GF, Sandford RN, Jones DE, Nakamura M, Ueno K, Hitomi Y, Kawashima M, Nishida N, Tokunaga K, Nagasaki M, Tanaka A, Tang R, Li Z, Shi Y, Liu X, Xiong M, Hirschfield G, Siminovitch KA, Canadian-US PBC Consortium, Italian PBC Genetics Study Group, UK-PBC Consortium, Japan PBC-GWAS Consortium, Carbone M, Cardamone G, Duga S, Gershwin ME, Seldin MF, Invernizzi P, and LiveR North

Subjects
Canadian-US PBC Consortium, 0301 basic medicine, Male, Linkage disequilibrium, Genome-wide association study, Disease, PBC, Settore MED/03 - GENETICA MEDICA, Linkage Disequilibrium, 0302 clinical medicine, UK-PBC Consortium, Genotype, Mitochondrial Precursor Protein Import Complex Proteins, Italian PBC Genetics Study Group, Odds Ratio, X-Wide Association Study, Japan PBC-GWAS Consortium, X chromosome, Genetics, Liver Cirrhosis, Biliary, Gastroenterology, Forkhead Transcription Factors, DNA-Binding Proteins, Shal Potassium Channels, 030211 gastroenterology & hepatology, Female, Adult, Monosaccharide Transport Proteins, Superenhancer, Locus (genetics), Single-nucleotide polymorphism, Biology, Protein Serine-Threonine Kinases, Polymorphism, Single Nucleotide, Article, White People, 03 medical and health sciences, Asian People, Proto-Oncogene Proteins, Endopeptidases, Humans, Cell Lineage, Genetic Predisposition to Disease, Meta-analysi, Genetic association, Chromosomes, Human, X, Gastroenterology & Hepatology, Hepatology, 1103 Clinical Sciences, Meta-analysis, 030104 developmental biology, Genetic Loci, 1114 Paediatrics and Reproductive Medicine, 1109 Neurosciences, Carrier Proteins, Genome-Wide Association Study
Abstract

Background & aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09-1.26; P = 9.93 × 10-8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 × 10-9; OR, 1.33; 95% CI, 1.21-1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). Conclusions: This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus.

Published
2021

5. An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs

Author

Heather J. Cordell, James J. Fryett, Kazuko Ueno, Rebecca Darlay, Yoshihiro Aiba, Yuki Hitomi, Minae Kawashima, Nao Nishida, Seik-Soon Khor, Olivier Gervais, Yosuke Kawai, Masao Nagasaki, Katsushi Tokunaga, Ruqi Tang, Yongyong Shi, Zhiqiang Li, Brian D. Juran, Elizabeth J. Atkinson, Alessio Gerussi, Marco Carbone, Rosanna Asselta, Angela Cheung, Mariza de Andrade, Aris Baras, Julie Horowitz, Manuel A.R. Ferreira, Dylan Sun, David E. Jones, Steven Flack, Ann Spicer, Victoria L. Mulcahy, Jinyoung Byan, Younghun Han, Richard N. Sandford, Konstantinos N. Lazaridis, Christopher I. Amos, Gideon M. Hirschfield, Michael F. Seldin, Pietro Invernizzi, Katherine A. Siminovitch, Xiong Ma, Minoru Nakamura, George F. Mells, Andrew Mason, Catherine Vincent, Gang Xie, Jinyi Zhang, Andrea Affronti, Piero L. Almasio, Domenico Alvaro, Pietro Andreone, Angelo Andriulli, Francesco Azzaroli, Pier Maria Battezzati, Antonio Benedetti, MariaConsiglia Bragazzi, Maurizia Brunetto, Savino Bruno, Vincenza Calvaruso, Vincenzo Cardinale, Giovanni Casella, Nora Cazzagon, Antonio Ciaccio, Barbara Coco, Agostino Colli, Guido Colloredo, Massimo Colombo, Silvia Colombo, Laura Cristoferi, Carmela Cursaro, Lory Saveria Crocè, Andrea Crosignani, Daphne D’Amato, Francesca Donato, Gianfranco Elia, Luca Fabris, Stefano Fagiuoli, Carlo Ferrari, Annarosa Floreani, Andrea Galli, Edoardo Giannini, Ignazio Grattagliano, Pietro Lampertico, Ana Lleo, Federica Malinverno, Clara Mancuso, Fabio Marra, Marco Marzioni, Sara Massironi, Alberto Mattalia, Luca Miele, Chiara Milani, Lorenzo Morini, Filomena Morisco, Luigi Muratori, Paolo Muratori, Grazia A. Niro, Sarah O’Donnell, Antonio Picciotto, Piero Portincasa, Cristina Rigamonti, Vincenzo Ronca, Floriano Rosina, Giancarlo Spinzi, Mario Strazzabosco, Mirko Tarocchi, Claudio Tiribelli, Pierluigi Toniutto, Luca Valenti, Maria Vinci, Massimo Zuin, Hitomi Nakamura, Seigo Abiru, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi, Hiromi Ishibashi, Masahiro Ito, Kiyoshi Migita, Hiromasa Ohira, Shinji Katsushima, Atsushi Naganuma, Kazuhiro Sugi, Tatsuji Komatsu, Tomohiko Mannami, Kouki Matsushita, Kaname Yoshizawa, Fujio Makita, Toshiki Nikami, Hideo Nishimura, Hiroshi Kouno, Hirotaka Kouno, Hajime Ota, Takuya Komura, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Keisuke Ario, Makoto Nakamuta, Tsutomu Yamashita, Kiyoshi Furuta, Masahiro Kikuchi, Noriaki Naeshiro, Hironao Takahashi, Yutaka Mano, Seiji Tsunematsu, Iwao Yabuuchi, Yusuke Shimada, Kazuhiko Yamauchi, Rie Sugimoto, Hironori Sakai, Eiji Mita, Masaharu Koda, Satoru Tsuruta, Hiroshi Kamitsukasa, Takeaki Sato, Naohiko Masaki, Tatsuro Kobata, Nobuyoshi Fukushima, Yukio Ohara, Toyokichi Muro, Eiichi Takesaki, Hitoshi Takaki, Tetsuo Yamamoto, Michio Kato, Yuko Nagaoki, Shigeki Hayashi, Jinya Ishida, Yukio Watanabe, Masakazu Kobayashi, Michiaki Koga, Takeo Saoshiro, Michiyasu Yagura, Keisuke Hirata, Atsushu Tanaka, Hajime Takikawa, Mikio Zeniya, Masanori Abe, Morikazu Onji, Shuichi Kaneko, Masao Honda, Kuniaki Arai, Teruko Arinaga-Hino, Etsuko Hashimoto, Makiko Taniai, Takeji Umemura, Satoru Joshita, Kazuhiko Nakao, Tatsuki Ichikawa, Hidetaka Shibata, Satoshi Yamagiwa, Masataka Seike, Koichi Honda, Shotaro Sakisaka, Yasuaki Takeyama, Masaru Harada, Michio Senju, Osamu Yokosuka, Tatsuo Kanda, Yoshiyuki Ueno, Kentaro Kikuchi, Hirotoshi Ebinuma, Takashi Himoto, Michio Yasunami, Kazumoto Murata, Masashi Mizokami, Kazuhito Kawata, Shinji Shimoda, Yasuhiro Miyake, Akinobu Takaki, Kazuhide Yamamoto, Katsuji Hirano, Takafumi Ichida, Akio Ido, Hirohito Tsubouchi, Kazuaki Chayama, Kenichi Harada, Yasuni Nakanuma, Yoshihiko Maehara, Akinobu Taketomi, Ken Shirabe, Yuji Soejima, Akira Mori, Shintaro Yagi, Shinji Uemoto, Egawa H, Tomohiro Tanaka, Noriyo Yamashiki, Sumito Tamura, Yasuhiro Sugawara, Norihiro Kokudo, Naga Chalasani, Vel Luketic, Joseph Odin, Kapil Chopra, Goncalo Abecasis, Michael Cantor, Giovanni Coppola, Aris Economides, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Thomas D. Schleicher, Maria Sotiropoulos Padilla, Karina Toledo, Louis Widom, Sarah E. Wolf, Manasi Pradhan, Kia Manoochehri, Ricardo H. Ulloa, Xiaodong Bai, Suganthi Balasubramanian, Leland Barnard, Andrew Blumenfeld, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Evan K. Maxwell, William Salerno, Jeffrey C. Staples, Marcus B. Jones, Lyndon J. Mitnaul, Richard Sturgess, Christopher Healey, Andrew Yeoman, Anton VJ. Gunasekera, Paul Kooner, Kapil Kapur, V. Sathyanarayana, Yiannis Kallis, Javaid Subhani, Rory Harvey, Roger McCorry, Paul Rooney, David Ramanaden, Richard Evans, Thiriloganathan Mathialahan, Jaber Gasem, Christopher Shorrock, Mahesh Bhalme, Paul Southern, Jeremy A. Tibble, David A. Gorard, Susan Jones, George Mells, Victoria Mulcahy, Brijesh Srivastava, Matthew R. Foxton, Carole E. Collins, David Elphick, Mazn Karmo, Francisco Porras-Perez, Michael Mendall, Tom Yapp, Minesh Patel, Roland Ede, Joanne Sayer, James Jupp, Neil Fisher, Martyn J. Carter, Konrad Koss, Jayshri Shah, Andrzej Piotrowicz, Glyn Scott, Charles Grimley, Ian R. Gooding, Simon Williams, Judith Tidbury, Guan Lim, Kuldeep Cheent, Sass Levi, Dina Mansour, Matilda Beckley, Coral Hollywood, Terry Wong, Richard Marley, John Ramage, Harriet M. Gordon, Jo Ridpath, Theodore Ngatchu, Vijay Paul Bob Grover, Ray G. Shidrawi, George Abouda, L. Corless, Mark Narain, Ian Rees, Ashley Brown, Simon Taylor-Robinson, Joy Wilkins, Leonie Grellier, Paul Banim, Debasish Das, Michael A. Heneghan, Howard Curtis, Helen C. Matthews, Faiyaz Mohammed, Mark Aldersley, Raj Srirajaskanthan, Giles Walker, Alistair McNair, Amar Sharif, Sambit Sen, George Bird, Martin I. Prince, Geeta Prasad, Paul Kitchen, Adrian Barnardo, Chirag Oza, Nurani N. Sivaramakrishnan, Prakash Gupta, Amir Shah, Chris DJ. Evans, Subrata Saha, Katharine Pollock, Peter Bramley, Ashis Mukhopadhya, Stephen T. Barclay, Natasha McDonald, Andrew J. Bathgate, Kelvin Palmer, John F. Dillon, Simon M. Rushbrook, Robert Przemioslo, Chris McDonald, Andrew Millar, Cheh Tai, Stephen Mitchell, Jane Metcalf, Syed Shaukat, Mary Ninkovic, Udi Shmueli, Andrew Davis, Asifabbas Naqvi, Tom JW. Lee, Stephen Ryder, Jane Collier, Howard Klass, Matthew E. Cramp, Nichols Sharer, Richard Aspinall, Deb Ghosh, Andrew C. Douds, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Steven Mann, Douglas Thorburn, Aileen Marshall, Imran Patanwala, Aftab Ala, Julia Maltby, Ray Matthew, Chris Corbett, Sam Vyas, Saket Singhal, Dermot Gleeson, Sharat Misra, Jeff Butterworth, Keith George, Tim Harding, Andrew Douglass, Harriet Mitchison, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Graham Butcher, Daniel Forton, Zahid Mahmood, Matthew Cowan, Debashis Das, Chin Lye Ch’ng, Mesbah Rahman, Gregory C.A. Whatley, Emma Wesley, Aditya Mandal, Sanjiv Jain, Stephen P. Pereira, Mark Wright, Palak Trivedi, Fiona H. Gordon, Esther Unitt, Altaf Palejwala, Andrew Austin, Vishwaraj Vemala, Allister Grant, Andrew D. Higham, Alison Brind, Ray Mathew, Mark Cox, Subramaniam Ramakrishnan, Alistair King, Simon Whalley, Jocelyn Fraser, S.J. Thomson, Andrew Bell, Voi Shim Wong, Richard Kia, Ian Gee, Richard Keld, Rupert Ransford, James Gotto, Charles Millson, Cordell, H. J., Fryett, J. J., Ueno, K., Darlay, R., Aiba, Y., Hitomi, Y., Kawashima, M., Nishida, N., Khor, S. -S., Gervais, O., Kawai, Y., Nagasaki, M., Tokunaga, K., Tang, R., Shi, Y., Li, Z., Juran, B. D., Atkinson, E. J., Gerussi, A., Carbone, M., Asselta, R., Cheung, A., de Andrade, M., Baras, A., Horowitz, J., Ferreira, M. A. R., Sun, D., Jones, D. E., Flack, S., Spicer, A., Mulcahy, V. L., Byan, J., Han, Y., Sandford, R. N., Lazaridis, K. N., Amos, C. I., Hirschfield, G. M., Seldin, M. F., Invernizzi, P., Siminovitch, K. A., Ma, X., Nakamura, M., Mells, G. F., Mason, A., Vincent, C., Xie, G., Zhang, J., Affronti, A., Almasio, P. L., Alvaro, D., Andreone, P., Andriulli, A., Azzaroli, F., Battezzati, P. M., Benedetti, A., Bragazzi, M., Brunetto, M., Bruno, S., Calvaruso, V., Cardinale, V., Casella, G., Cazzagon, N., Ciaccio, A., Coco, B., Colli, A., Colloredo, G., Colombo, M., Colombo, S., Cristoferi, L., Cursaro, C., Croce, L. S., Crosignani, A., D'Amato, D., Donato, F., Elia, G., Fabris, L., Fagiuoli, S., Ferrari, C., Floreani, A., Galli, A., Giannini, E., Grattagliano, I., Lampertico, P., Lleo, A., Malinverno, F., Mancuso, C., Marra, F., Marzioni, M., Massironi, S., Mattalia, A., Miele, L., Milani, C., Morini, L., Morisco, F., Muratori, L., Muratori, P., Niro, G. A., O'Donnell, S., Picciotto, A., Portincasa, P., Rigamonti, C., Ronca, V., Rosina, F., Spinzi, G., Strazzabosco, M., Tarocchi, M., Tiribelli, C., Toniutto, P., Valenti, L., Vinci, M., Zuin, M., Nakamura, H., Abiru, S., Nagaoka, S., Komori, A., Yatsuhashi, H., Ishibashi, H., Ito, M., Migita, K., Ohira, H., Katsushima, S., Naganuma, A., Sugi, K., Komatsu, T., Mannami, T., Matsushita, K., Yoshizawa, K., Makita, F., Nikami, T., Nishimura, H., Kouno, H., Ota, H., Komura, T., Nakamura, Y., Shimada, M., Hirashima, N., Komeda, T., Ario, K., Nakamuta, M., Yamashita, T., Furuta, K., Kikuchi, M., Naeshiro, N., Takahashi, H., Mano, Y., Tsunematsu, S., Yabuuchi, I., Shimada, Y., Yamauchi, K., Sugimoto, R., Sakai, H., Mita, E., Koda, M., Tsuruta, S., Kamitsukasa, H., Sato, T., Masaki, N., Kobata, T., Fukushima, N., Ohara, Y., Muro, T., Takesaki, E., Takaki, H., Yamamoto, T., Kato, M., Nagaoki, Y., Hayashi, S., Ishida, J., Watanabe, Y., Kobayashi, M., Koga, M., Saoshiro, T., Yagura, M., Hirata, K., Tanaka, A., Takikawa, H., Zeniya, M., Abe, M., Onji, M., Kaneko, S., Honda, M., Arai, K., Arinaga-Hino, T., Hashimoto, E., Taniai, M., Umemura, T., Joshita, S., Nakao, K., Ichikawa, T., Shibata, H., Yamagiwa, S., Seike, M., Honda, K., Sakisaka, S., Takeyama, Y., Harada, M., Senju, M., Yokosuka, O., Kanda, T., Ueno, Y., Kikuchi, K., Ebinuma, H., Himoto, T., Yasunami, M., Murata, K., Mizokami, M., Kawata, K., Shimoda, S., Miyake, Y., Takaki, A., Yamamoto, K., Hirano, K., Ichida, T., Ido, A., Tsubouchi, H., Chayama, K., Harada, K., Nakanuma, Y., Maehara, Y., Taketomi, A., Shirabe, K., Soejima, Y., Mori, A., Yagi, S., Uemoto, S., H, E., Tanaka, T., Yamashiki, N., Tamura, S., Sugawara, Y., Kokudo, N., Chalasani, N., Luketic, V., Odin, J., Chopra, K., Abecasis, G., Cantor, M., Coppola, G., Economides, A., Lotta, L. A., Overton, J. D., Reid, J. G., Shuldiner, A., Beechert, C., Forsythe, C., Fuller, E. D., Gu, Z., Lattari, M., Lopez, A., Schleicher, T. D., Padilla, M. S., Toledo, K., Widom, L., Wolf, S. E., Pradhan, M., Manoochehri, K., Ulloa, R. H., Bai, X., Balasubramanian, S., Barnard, L., Blumenfeld, A., Eom, G., Habegger, L., Hawes, A., Khalid, S., Maxwell, E. K., Salerno, W., Staples, J. C., Jones, M. B., Mitnaul, L. J., Sturgess, R., Healey, C., Yeoman, A., Gunasekera, A. V., Kooner, P., Kapur, K., Sathyanarayana, V., Kallis, Y., Subhani, J., Harvey, R., Mccorry, R., Rooney, P., Ramanaden, D., Evans, R., Mathialahan, T., Gasem, J., Shorrock, C., Bhalme, M., Southern, P., Tibble, J. A., Gorard, D. A., Jones, S., Mells, G., Mulcahy, V., Srivastava, B., Foxton, M. R., Collins, C. E., Elphick, D., Karmo, M., Porras-Perez, F., Mendall, M., Yapp, T., Patel, M., Ede, R., Sayer, J., Jupp, J., Fisher, N., Carter, M. J., Koss, K., Shah, J., Piotrowicz, A., Scott, G., Grimley, C., Gooding, I. R., Williams, S., Tidbury, J., Lim, G., Cheent, K., Levi, S., Mansour, D., Beckley, M., Hollywood, C., Wong, T., Marley, R., Ramage, J., Gordon, H. M., Ridpath, J., Ngatchu, T., Bob Grover, V. P., Shidrawi, R. G., Abouda, G., Corless, L., Narain, M., Rees, I., Brown, A., Taylor-Robinson, S., Wilkins, J., Grellier, L., Banim, P., Das, D., Heneghan, M. A., Curtis, H., Matthews, H. C., Mohammed, F., Aldersley, M., Srirajaskanthan, R., Walker, G., Mcnair, A., Sharif, A., Sen, S., Bird, G., Prince, M. I., Prasad, G., Kitchen, P., Barnardo, A., Oza, C., Sivaramakrishnan, N. N., Gupta, P., Shah, A., Evans, C. D., Saha, S., Pollock, K., Bramley, P., Mukhopadhya, A., Barclay, S. T., Mcdonald, N., Bathgate, A. J., Palmer, K., Dillon, J. F., Rushbrook, S. M., Przemioslo, R., Mcdonald, C., Millar, A., Tai, C., Mitchell, S., Metcalf, J., Shaukat, S., Ninkovic, M., Shmueli, U., Davis, A., Naqvi, A., Lee, T. J., Ryder, S., Collier, J., Klass, H., Cramp, M. E., Sharer, N., Aspinall, R., Ghosh, D., Douds, A. C., Booth, J., Williams, E., Hussaini, H., Christie, J., Mann, S., Thorburn, D., Marshall, A., Patanwala, I., Ala, A., Maltby, J., Matthew, R., Corbett, C., Vyas, S., Singhal, S., Gleeson, D., Misra, S., Butterworth, J., George, K., Harding, T., Douglass, A., Mitchison, H., Panter, S., Shearman, J., Bray, G., Roberts, M., Butcher, G., Forton, D., Mahmood, Z., Cowan, M., Ch'Ng, C. L., Rahman, M., Whatley, G. C. A., Wesley, E., Mandal, A., Jain, S., Pereira, S. P., Wright, M., Trivedi, P., Gordon, F. H., Unitt, E., Palejwala, A., Austin, A., Vemala, V., Grant, A., Higham, A. D., Brind, A., Mathew, R., Cox, M., Ramakrishnan, S., King, A., Whalley, S., Fraser, J., Thomson, S. J., Bell, A., Wong, V. S., Kia, R., Gee, I., Keld, R., Ransford, R., Gotto, J., Millson, C., Cordell H.J., Fryett J.J., Ueno K., Darlay R., Aiba Y., Hitomi Y., Kawashima M., Nishida N., Khor S.-S., Gervais O., Kawai Y., Nagasaki M., Tokunaga K., Tang R., Shi Y., Li Z., Juran B.D., Atkinson E.J., Gerussi A., Carbone M., Asselta R., Cheung A., de Andrade M., Baras A., Horowitz J., Ferreira M.A.R., Sun D., Jones D.E., Flack S., Spicer A., Mulcahy V.L., Byan J., Han Y., Sandford R.N., Lazaridis K.N., Amos C.I., Hirschfield G.M., Seldin M.F., Invernizzi P., Siminovitch K.A., Ma X., Nakamura M., Mells G.F., Mason A., Vincent C., Xie G., Zhang J., Affronti A., Almasio P.L., Alvaro D., Andreone P., Andriulli A., Azzaroli F., Battezzati P.M., Benedetti A., Bragazzi M., Brunetto M., Bruno S., Calvaruso V., Cardinale V., Casella G., Cazzagon N., Ciaccio A., Coco B., Colli A., Colloredo G., Colombo M., Colombo S., Cristoferi L., Cursaro C., Croce L.S., Crosignani A., D'Amato D., Donato F., Elia G., Fabris L., Fagiuoli S., Ferrari C., Floreani A., Galli A., Giannini E., Grattagliano I., Lampertico P., Lleo A., Malinverno F., Mancuso C., Marra F., Marzioni M., Massironi S., Mattalia A., Miele L., Milani C., Morini L., Morisco F., Muratori L., Muratori P., Niro G.A., O'Donnell S., Picciotto A., Portincasa P., Rigamonti C., Ronca V., Rosina F., Spinzi G., Strazzabosco M., Tarocchi M., Tiribelli C., Toniutto P., Valenti L., Vinci M., Zuin M., Nakamura H., Abiru S., Nagaoka S., Komori A., Yatsuhashi H., Ishibashi H., Ito M., Migita K., Ohira H., Katsushima S., Naganuma A., Sugi K., Komatsu T., Mannami T., Matsushita K., Yoshizawa K., Makita F., Nikami T., Nishimura H., Kouno H., Ota H., Komura T., Nakamura Y., Shimada M., Hirashima N., Komeda T., Ario K., Nakamuta M., Yamashita T., Furuta K., Kikuchi M., Naeshiro N., Takahashi H., Mano Y., Tsunematsu S., Yabuuchi I., Shimada Y., Yamauchi K., Sugimoto R., Sakai H., Mita E., Koda M., Tsuruta S., Kamitsukasa H., Sato T., Masaki N., Kobata T., Fukushima N., Ohara Y., Muro T., Takesaki E., Takaki H., Yamamoto T., Kato M., Nagaoki Y., Hayashi S., Ishida J., Watanabe Y., Kobayashi M., Koga M., Saoshiro T., Yagura M., Hirata K., Tanaka A., Takikawa H., Zeniya M., Abe M., Onji M., Kaneko S., Honda M., Arai K., Arinaga-Hino T., Hashimoto E., Taniai M., Umemura T., Joshita S., Nakao K., Ichikawa T., Shibata H., Yamagiwa S., Seike M., Honda K., Sakisaka S., Takeyama Y., Harada M., Senju M., Yokosuka O., Kanda T., Ueno Y., Kikuchi K., Ebinuma H., Himoto T., Yasunami M., Murata K., Mizokami M., Kawata K., Shimoda S., Miyake Y., Takaki A., Yamamoto K., Hirano K., Ichida T., Ido A., Tsubouchi H., Chayama K., Harada K., Nakanuma Y., Maehara Y., Taketomi A., Shirabe K., Soejima Y., Mori A., Yagi S., Uemoto S., H E., Tanaka T., Yamashiki N., Tamura S., Sugawara Y., Kokudo N., Chalasani N., Luketic V., Odin J., Chopra K., Abecasis G., Cantor M., Coppola G., Economides A., Lotta L.A., Overton J.D., Reid J.G., Shuldiner A., Beechert C., Forsythe C., Fuller E.D., Gu Z., Lattari M., Lopez A., Schleicher T.D., Padilla M.S., Toledo K., Widom L., Wolf S.E., Pradhan M., Manoochehri K., Ulloa R.H., Bai X., Balasubramanian S., Barnard L., Blumenfeld A., Eom G., Habegger L., Hawes A., Khalid S., Maxwell E.K., Salerno W., Staples J.C., Jones M.B., Mitnaul L.J., Sturgess R., Healey C., Yeoman A., Gunasekera A.V., Kooner P., Kapur K., Sathyanarayana V., Kallis Y., Subhani J., Harvey R., McCorry R., Rooney P., Ramanaden D., Evans R., Mathialahan T., Gasem J., Shorrock C., Bhalme M., Southern P., Tibble J.A., Gorard D.A., Jones S., Mells G., Mulcahy V., Srivastava B., Foxton M.R., Collins C.E., Elphick D., Karmo M., Porras-Perez F., Mendall M., Yapp T., Patel M., Ede R., Sayer J., Jupp J., Fisher N., Carter M.J., Koss K., Shah J., Piotrowicz A., Scott G., Grimley C., Gooding I.R., Williams S., Tidbury J., Lim G., Cheent K., Levi S., Mansour D., Beckley M., Hollywood C., Wong T., Marley R., Ramage J., Gordon H.M., Ridpath J., Ngatchu T., Bob Grover V.P., Shidrawi R.G., Abouda G., Corless L., Narain M., Rees I., Brown A., Taylor-Robinson S., Wilkins J., Grellier L., Banim P., Das D., Heneghan M.A., Curtis H., Matthews H.C., Mohammed F., Aldersley M., Srirajaskanthan R., Walker G., McNair A., Sharif A., Sen S., Bird G., Prince M.I., Prasad G., Kitchen P., Barnardo A., Oza C., Sivaramakrishnan N.N., Gupta P., Shah A., Evans C.D., Saha S., Pollock K., Bramley P., Mukhopadhya A., Barclay S.T., McDonald N., Bathgate A.J., Palmer K., Dillon J.F., Rushbrook S.M., Przemioslo R., McDonald C., Millar A., Tai C., Mitchell S., Metcalf J., Shaukat S., Ninkovic M., Shmueli U., Davis A., Naqvi A., Lee T.J., Ryder S., Collier J., Klass H., Cramp M.E., Sharer N., Aspinall R., Ghosh D., Douds A.C., Booth J., Williams E., Hussaini H., Christie J., Mann S., Thorburn D., Marshall A., Patanwala I., Ala A., Maltby J., Matthew R., Corbett C., Vyas S., Singhal S., Gleeson D., Misra S., Butterworth J., George K., Harding T., Douglass A., Mitchison H., Panter S., Shearman J., Bray G., Roberts M., Butcher G., Forton D., Mahmood Z., Cowan M., Ch'ng C.L., Rahman M., Whatley G.C.A., Wesley E., Mandal A., Jain S., Pereira S.P., Wright M., Trivedi P., Gordon F.H., Unitt E., Palejwala A., Austin A., Vemala V., Grant A., Higham A.D., Brind A., Mathew R., Cox M., Ramakrishnan S., King A., Whalley S., Fraser J., Thomson S.J., Bell A., Wong V.S., Kia R., Gee I., Keld R., Ransford R., Gotto J., Millson C., Medical Research Council (MRC), LiveR North, Cordell, H, Fryett, J, Ueno, K, Darlay, R, Aiba, Y, Hitomi, Y, Kawashima, M, Nishida, N, Khor, S, Gervais, O, Kawai, Y, Nagasaki, M, Tokunaga, K, Tang, R, Shi, Y, Li, Z, Juran, B, Atkinson, E, Gerussi, A, Carbone, M, Asselta, R, Cheung, A, de Andrade, M, Baras, A, Horowitz, J, Ferreira, M, Sun, D, Jones, D, Flack, S, Spicer, A, Mulcahy, V, Byan, J, Han, Y, Sandford, R, Lazaridis, K, Amos, C, Hirschfield, G, Seldin, M, Invernizzi, P, Siminovitch, K, Ma, X, Nakamura, M, Mells, G, Mason, A, Vincent, C, Xie, G, Zhang, J, Affronti, A, Almasio, P, Alvaro, D, Andreone, P, Andriulli, A, Azzaroli, F, Battezzati, P, Benedetti, A, Bragazzi, M, Brunetto, M, Bruno, S, Calvaruso, V, Cardinale, V, Casella, G, Cazzagon, N, Ciaccio, A, Coco, B, Colli, A, Colloredo, G, Colombo, M, Colombo, S, Cristoferi, L, Cursaro, C, Croce, L, Crosignani, A, D'Amato, D, Donato, F, Elia, G, Fabris, L, Fagiuoli, S, Ferrari, C, Floreani, A, Galli, A, Giannini, E, Grattagliano, I, Lampertico, P, Lleo, A, Malinverno, F, Mancuso, C, Marra, F, Marzioni, M, Massironi, S, Mattalia, A, Miele, L, Milani, C, Morini, L, Morisco, F, Muratori, L, Muratori, P, Niro, G, O'Donnell, S, Picciotto, A, Portincasa, P, Rigamonti, C, Ronca, V, Rosina, F, Spinzi, G, Strazzabosco, M, Tarocchi, M, Tiribelli, C, Toniutto, P, Valenti, L, Vinci, M, Zuin, M, Nakamura, H, Abiru, S, Nagaoka, S, Komori, A, Yatsuhashi, H, Ishibashi, H, Ito, M, Migita, K, Ohira, H, Katsushima, S, Naganuma, A, Sugi, K, Komatsu, T, Mannami, T, Matsushita, K, Yoshizawa, K, Makita, F, Nikami, T, Nishimura, H, Kouno, H, Ota, H, Komura, T, Nakamura, Y, Shimada, M, Hirashima, N, Komeda, T, Ario, K, Nakamuta, M, Yamashita, T, Furuta, K, Kikuchi, M, Naeshiro, N, Takahashi, H, Mano, Y, Tsunematsu, S, Yabuuchi, I, Shimada, Y, Yamauchi, K, Sugimoto, R, Sakai, H, Mita, E, Koda, M, Tsuruta, S, Kamitsukasa, H, Sato, T, Masaki, N, Kobata, T, Fukushima, N, Ohara, Y, Muro, T, Takesaki, E, Takaki, H, Yamamoto, T, Kato, M, Nagaoki, Y, Hayashi, S, Ishida, J, Watanabe, Y, Kobayashi, M, Koga, M, Saoshiro, T, Yagura, M, Hirata, K, Tanaka, A, Takikawa, H, Zeniya, M, Abe, M, Onji, M, Kaneko, S, Honda, M, Arai, K, Arinaga-Hino, T, Hashimoto, E, Taniai, M, Umemura, T, Joshita, S, Nakao, K, Ichikawa, T, Shibata, H, Yamagiwa, S, Seike, M, Honda, K, Sakisaka, S, Takeyama, Y, Harada, M, Senju, M, Yokosuka, O, Kanda, T, Ueno, Y, Kikuchi, K, Ebinuma, H, Himoto, T, Yasunami, M, Murata, K, Mizokami, M, Kawata, K, Shimoda, S, Miyake, Y, Takaki, A, Yamamoto, K, Hirano, K, Ichida, T, Ido, A, Tsubouchi, H, Chayama, K, Harada, K, Nakanuma, Y, Maehara, Y, Taketomi, A, Shirabe, K, Soejima, Y, Mori, A, Yagi, S, Uemoto, S, H, E, Tanaka, T, Yamashiki, N, Tamura, S, Sugawara, Y, Kokudo, N, Chalasani, N, Luketic, V, Odin, J, Chopra, K, Abecasis, G, Cantor, M, Coppola, G, Economides, A, Lotta, L, Overton, J, Reid, J, Shuldiner, A, Beechert, C, Forsythe, C, Fuller, E, Gu, Z, Lattari, M, Lopez, A, Schleicher, T, Padilla, M, Toledo, K, Widom, L, Wolf, S, Pradhan, M, Manoochehri, K, Ulloa, R, Bai, X, Balasubramanian, S, Barnard, L, Blumenfeld, A, Eom, G, Habegger, L, Hawes, A, Khalid, S, Maxwell, E, Salerno, W, Staples, J, Jones, M, Mitnaul, L, Sturgess, R, Healey, C, Yeoman, A, Gunasekera, A, Kooner, P, Kapur, K, Sathyanarayana, V, Kallis, Y, Subhani, J, Harvey, R, Mccorry, R, Rooney, P, Ramanaden, D, Evans, R, Mathialahan, T, Gasem, J, Shorrock, C, Bhalme, M, Southern, P, Tibble, J, Gorard, D, Jones, S, Srivastava, B, Foxton, M, Collins, C, Elphick, D, Karmo, M, Porras-Perez, F, Mendall, M, Yapp, T, Patel, M, Ede, R, Sayer, J, Jupp, J, Fisher, N, Carter, M, Koss, K, Shah, J, Piotrowicz, A, Scott, G, Grimley, C, Gooding, I, Williams, S, Tidbury, J, Lim, G, Cheent, K, Levi, S, Mansour, D, Beckley, M, Hollywood, C, Wong, T, Marley, R, Ramage, J, Gordon, H, Ridpath, J, Ngatchu, T, Bob Grover, V, Shidrawi, R, Abouda, G, Corless, L, Narain, M, Rees, I, Brown, A, Taylor-Robinson, S, Wilkins, J, Grellier, L, Banim, P, Das, D, Heneghan, M, Curtis, H, Matthews, H, Mohammed, F, Aldersley, M, Srirajaskanthan, R, Walker, G, Mcnair, A, Sharif, A, Sen, S, Bird, G, Prince, M, Prasad, G, Kitchen, P, Barnardo, A, Oza, C, Sivaramakrishnan, N, Gupta, P, Shah, A, Evans, C, Saha, S, Pollock, K, Bramley, P, Mukhopadhya, A, Barclay, S, Mcdonald, N, Bathgate, A, Palmer, K, Dillon, J, Rushbrook, S, Przemioslo, R, Mcdonald, C, Millar, A, Tai, C, Mitchell, S, Metcalf, J, Shaukat, S, Ninkovic, M, Shmueli, U, Davis, A, Naqvi, A, Lee, T, Ryder, S, Collier, J, Klass, H, Cramp, M, Sharer, N, Aspinall, R, Ghosh, D, Douds, A, Booth, J, Williams, E, Hussaini, H, Christie, J, Mann, S, Thorburn, D, Marshall, A, Patanwala, I, Ala, A, Maltby, J, Matthew, R, Corbett, C, Vyas, S, Singhal, S, Gleeson, D, Misra, S, Butterworth, J, George, K, Harding, T, Douglass, A, Mitchison, H, Panter, S, Shearman, J, Bray, G, Roberts, M, Butcher, G, Forton, D, Mahmood, Z, Cowan, M, Ch'Ng, C, Rahman, M, Whatley, G, Wesley, E, Mandal, A, Jain, S, Pereira, S, Wright, M, Trivedi, P, Gordon, F, Unitt, E, Palejwala, A, Austin, A, Vemala, V, Grant, A, Higham, A, Brind, A, Mathew, R, Cox, M, Ramakrishnan, S, King, A, Whalley, S, Fraser, J, Thomson, S, Bell, A, Wong, V, Kia, R, Gee, I, Keld, R, Ransford, R, Gotto, J, Millson, C, Cordell HJ, Fryett JJ, Ueno K, Darlay R, Aiba Y, Hitomi Y, Kawashima M, Nishida N, Khor SS, Gervais O, Kawai Y, Nagasaki M, Tokunaga K, Tang R, Shi Y, Li Z, Juran BD, Atkinson EJ, Gerussi A, Carbone M, Asselta R, Cheung A, de Andrade M, Baras A, Horowitz J, Ferreira MAR, Sun D, Jones DE, Flack S, Spicer A, Mulcahy VL, Byan J, Han Y, Sandford RN, Lazaridis KN, Amos CI, Hirschfield GM, Seldin MF, Invernizzi P, Siminovitch KA, Ma X, Nakamura M, Mells GF, PBC Consortia, Canadian PBC Consortium, Chinese PBC Consortium, Italian PBC Study Group, Japan-PBC-GWAS Consortium, US PBC Consortium, UK-PBC Consortium, and Calvaruso V. .

Subjects
Liver Cirrhosis, ALSPAC, ERN RARE-LIVER, Genomic co-localization, Network-based in silico drug efficacy screening, UK-PBC, 0301 basic medicine, Candidate gene, Genome-Wide Association Study, Humans, Liver Cirrhosis, Biliary, Italian PBC Study Group, LD SCORE REGRESSION, Japan-PBC-GWAS Consortium, Genome-wide association study, Locus (genetics), Disease, SUSCEPTIBILITY, PBC, Chronic liver disease, Bioinformatics, GENETIC ASSOCIATION, 1117 Public Health and Health Services, 03 medical and health sciences, 0302 clinical medicine, UK-PBC Consortium, Genotype, Medicine, Genetic association, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, Biliary, Chinese PBC Consortium, 1103 Clinical Sciences, medicine.disease, PBC Consortia, 030104 developmental biology, Meta-analysis, ERN RARE LIVER, 030211 gastroenterology & hepatology, US PBC Consortium, Canadian PBC Consortium, business, Life Sciences & Biomedicine, Human
Abstract

[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 772 controls from five European and two East Asian cohorts. [RESULTS] We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, each having key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, Jak-STAT signalling, and differentiation of TH1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some well-established in the treatment of other autoimmune disorders. [CONCLUSIONS] This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. [Lay summary] Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10, 516 people with PBC and 20, 772 healthy individuals recruited in Canada, China, Italy, Japan, UK, or USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these ‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC., 原発性胆汁性胆管炎のゲノムワイド関連解析 --国際メタ解析による新規疾患感受性遺伝子と治療薬候補の同定--. 京都大学プレスリリース. 2021-06-28.

Published
2021

6. Stress and its causes in UK gastroenterologists: results of a national survey by the British Society of Gastroenterology

Author

Howard Ellison, Andrew Goddard, Andrew C. Douds, Christopher O’Shea, Tony C.K. Tham, and Dermot Gleeson

Subjects
medicine.medical_specialty, Hepatology, business.industry, media_common.quotation_subject, Gastroenterology, Workload, medicine.disease_cause, Stress level, 03 medical and health sciences, 0302 clinical medicine, Clinical work, Internal medicine, Stress (linguistics), medicine, Happiness, Psychological stress, 030211 gastroenterology & hepatology, 030212 general & internal medicine, business, Professional Matters, media_common
Abstract

AimEvaluation of stress and its causes in UK gastroenterologists,DesignQuestionnaire emailed to all 1932 medical members of the British Society of Gastroenterology.ResultsOf 567 respondents (29%), 107 (20%) graded their stress level as 4 or 5 out of 5. Stress levels correlated inversely with self-reported happiness levels (r=−0.60; pThe main causes of stress were excessive clinical work (ranked highest by 47% and most commonly patient-related administration), working conditions beyond control (ranked highest by 15% and most commonly inadequate information technology systems, workspace and secretarial staff) and conflict (ranked highest by 9%). Of eight potential factors, happiness with work showed the closest associations with overall happiness (positive) and overall stress (negative) levels. Talking to someone at work about stress was ranked difficult or impossible by 35%. The highest ranked suggested solutions were relief from some duties and mentoring.ConclusionsStress is common and has objective correlates in UK gastroenterologists. The main cause is excessive workload.

Published
2018
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7. Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial

Author

Stephen R. Lewis, Chris Haigh, Philip Mairs, Sean M. Kelly, Andrew Higham, Art Tucker, Stephen Gore, Michael Gibbons, Mark Whitehead, Krish Ragunath, Michael Hallissey, Howard Curtis, Simon D. Johnston, James Neale, Hugh Barr, Danielle Morris, Timothy Harding, William Dickey, Carrie Kelly, Sue Cullen, Michael A. Mendall, Robert Boulton-Jones, Neil Fisher, Peter Isaacs, Andrew Murdock, Naveen Sharma, Tawfique Daneshmend, Johan Rademaker, Bart Decadt, Bernhard Usselmann, Rebecca C. Fitzgerald, Christopher Macdonald, Vankatraman Sankara-Raman, Tamas Hickish, Sumesh Sukumaran, Andrew F Goddard, Ali S. Taha, Nigel Trudgill, Nicholas I. Church, Andrew C Douds, Cathryn Edwards, Claire Brooks, Martin Wadley, Sean L. Preston, Sherzad Balata, John Todd, Scott Sanders, A Soliman, Ian Perry, Mathis Heydtmann, Peter Watson, Mohammad Mesbahur Rahman, Rebecca Harrison, John de Caestecker, Susi Green, Peik Loon Lim, David Johnston, Yeng Ang, Perminder Phull, Janusz Jankowski, Julian Teare, Iqbal Ansary Khan, Paul Moayyedi, Stephen Jones, David Monk, Rupert Ransford, Haythem Ali, Ian D. Penman, Gavin Reilly, Graham Turner, Adam Stone, Adelyn Wise, Lucina Jackson, Colin Rodgers, Andrew Chilton, Giovanni Domenico Tebala, David Aldulaimi, Howard Smart, Mark Narain, Abduljalil Benhamida, Sharon Love, Bashir Rameh, Stewart J Campbell, Nick Maynard, Pradeep Bhandari, Tony C.K. Tham, Kishor Vaidya, Gareth Davies, Andrew I. Bell, Duncan Loft, Thomas Lee, Hisaharu Suzuki, Iain A. Murray, Grant Fullarton, Jason M. Dunn, James McLoughlin, Stirling Pugh, Ian Sargeant, Mark R Anderson, Stephen Attwood, Adam Haycock, and Joy Worthingon

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Population, Gastroenterology, Drug Administration Schedule, Article, Esomeprazole, Young Adult, 03 medical and health sciences, Barrett Esophagus, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Internal medicine, Metaplasia, medicine, Humans, Adverse effect, education, Aged, Aspirin, education.field_of_study, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Aspirin, Barrett’s oesophagus, cancer, chemoprevention, randomized clinical trial, proton pump inhibitors, Intestinal metaplasia, Proton Pump Inhibitors, General Medicine, Middle Aged, medicine.disease, 3. Good health, Dysplasia, 030220 oncology & carcinogenesis, Number needed to treat, Female, 030211 gastroenterology & hepatology, Drug Therapy, Combination, medicine.symptom, business, medicine.drug
Abstract

BACKGROUND: Oesophageal adenocarcinoma is the sixth most common cause of cancer death worldwide and Barrett's oesophagus is the biggest risk factor. We aimed to evaluate the efficacy of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for improving outcomes in patients with Barrett's oesophagus.METHODS: The Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial had a 2 × 2 factorial design and was done at 84 centres in the UK and one in Canada. Patients with Barrett's oesophagus of 1 cm or more were randomised 1:1:1:1 using a computer-generated schedule held in a central trials unit to receive high-dose (40 mg twice-daily) or low-dose (20 mg once-daily) PPI, with or without aspirin (300 mg per day in the UK, 325 mg per day in Canada) for at least 8 years, in an unblinded manner. Reporting pathologists were masked to treatment allocation. The primary composite endpoint was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, which was analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all patients in the intention-to-treat population. This trial is registered with EudraCT, number 2004-003836-77.FINDINGS: Between March 10, 2005, and March 1, 2009, 2557 patients were recruited. 705 patients were assigned to low-dose PPI and no aspirin, 704 to high-dose PPI and no aspirin, 571 to low-dose PPI and aspirin, and 577 to high-dose PPI and aspirin. Median follow-up and treatment duration was 8·9 years (IQR 8·2-9·8), and we collected 20 095 follow-up years and 99·9% of planned data. 313 primary events occurred. High-dose PPI (139 events in 1270 patients) was superior to low-dose PPI (174 events in 1265 patients; time ratio [TR] 1·27, 95% CI 1·01-1·58, p=0·038). Aspirin (127 events in 1138 patients) was not significantly better than no aspirin (154 events in 1142 patients; TR 1·24, 0·98-1·57, p=0·068). If patients using non-steroidal anti-inflammatory drugs were censored at the time of first use, aspirin was significantly better than no aspirin (TR 1·29, 1·01-1·66, p=0·043; n=2236). Combining high-dose PPI with aspirin had the strongest effect compared with low-dose PPI without aspirin (TR 1·59, 1·14-2·23, p=0·0068). The numbers needed to treat were 34 for PPI and 43 for aspirin. Only 28 (1%) participants reported study-treatment-related serious adverse events.INTERPRETATION: High-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett's oesophagus.FUNDING: Cancer Research UK, AstraZeneca, Wellcome Trust, and Health Technology Assessment.

Published
2018
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9. A rare clinical presentation of a malignant fibrous histiocytoma within the iliopsoas muscle

Author

Salah Hammouche, Tina Maheswaran, Andrew C. Douds, and Imran Mohammed

Subjects
Male, Muscle Neoplasms, Pathology, medicine.medical_specialty, Referred pain, Groin, Iliopsoas Muscle, business.industry, Histiocytoma, Malignant Fibrous, General Medicine, Middle Aged, On-line Case Report, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Humans, Medicine, Surgery, Sarcoma, Presentation (obstetrics), Iliopsoas, Tomography, X-Ray Computed, business, Psoas Muscles
Abstract

Primary malignant tumours of the iliopsoas compartment are rare clinical entities that are infrequently reported in the literature. Although presenting symptoms vary, this is a very uncommon report of referred pain to the groin and testicular region in a psoas muscle tumour.

Published
2010
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10. Serum intercellular adhesion molecule-1 in alcoholic liver disease and its relationship with histological disease severity

Author

A. Guan Lim, Riadh P. Jazrawi, Andrew C. Douds, J. Douglas Maxwell, and Caroline Finlayson

Subjects
Adult, Male, Alcoholic liver disease, Pathology, medicine.medical_specialty, Cirrhosis, Neopterin, chemistry.chemical_compound, Primary biliary cirrhosis, Biopsy, medicine, Humans, Liver Diseases, Alcoholic, Aged, Hepatology, medicine.diagnostic_test, business.industry, Beta-2 microglobulin, Middle Aged, Intercellular Adhesion Molecule-1, medicine.disease, Biopterin, chemistry, Female, Steatosis, beta 2-Microglobulin, business, Liver function tests
Abstract

Background: Infilitration of the liver by leukocytes is a histological feature of alcoholic liver disease. Intercellular adhesion molecule-1 (ICAM-1) mediates the migration of lymphocytes from the circulation to target sites of inflammation. It has been demonstrated in the liver of alcoholic liver disease subjects and as a circulating soluble form (sICAM-1). The origin of sICAM-1 and its relationship to disease severity is unknown, although it has been postulated that it may arise from activated T lymphocytes and is an inflammatory marker. Aims: The aim of the study was to determine the relationship of sICAM-1 to clinical and histological severity of alcoholic liver disease and toserum T-cell (soluble interleukin-2 receptor (sIL-2R), β 2 -microglobulin) and monocyte (neopterin) immune activation markers. Methods: Serum from 48 outpatients with biopsy proven alcoholic liver disease (steatosis=9, cirrhosis=28, hepatitis±cirrhosis=11), 31 with primary biliary cirrhosis and 27 normals was assayed for sICAM-1, sIL-2R, β 2 -microglobulin, and neopterin. Results: sICAM-1 was significantly elevated, p =0.0001, in alcoholic liver disease and primary biliary cirrhosis patients compared to normals. Circulating sIL-2R ( p =0.0001) and β 2 -miroglobulin ( p =0.0034) were significantly elevated in alcoholic liver disease compared to controls. There was a highly significant correlation between levels of sICAM-1 and histological grade of disease, Rs=0.80 ( p =0.0001), but no significant correlation with clinical correlates of disease severity of circulating immune activation markers. Conclusions: sICAM-1 is elevated in alcoholic liver disease, is a marker of histological severity of disease and does not appear to originate from activated T lymphocytes. Measurements of sICAM-1 may be useful in assessing histological severity of alcoholic liver disease.

Published
1997
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11. Small bowel obstruction induced by spontaneous partial deflation of an intragastric balloon

Author

Vinod S Hegade, Ruchit Sood, and Andrew C. Douds

Subjects
Jejunal Diseases, Male, medicine.medical_specialty, Morbidly obese, Balloon, Jejunum, Young Adult, Weight loss, medicine, Humans, Gastric Balloon, business.industry, Impaction, General Medicine, medicine.disease, Surgery, Obesity, Morbid, Bowel obstruction, Equipment failure, medicine.anatomical_structure, Online Case Report, Equipment Failure, medicine.symptom, business, Intestinal Obstruction
Abstract

The intragastric balloon (IGB) has been used for decades as a temporary measure for weight reduction in the morbidly obese. Serious complications related to the device remain rare. We present the case of a 23-year-old Caucasian man who developed signs of bowel obstruction following spontaneous partial deflation of an air filled IGB with subsequent migration and impaction in the jejunum. We discuss the role of the IGB in the treatment of obesity, side effects and the serious complications that can occur.

Published
2012

12. Soluble intercellular adhesion molecule-1 in primary biliary cirrhosis: Relationship with disease stage, immune activity and cholestasis

Author

A. Guan Lim, Andrew C. Douds, Massimo Zuin, Riadh P. Jazrawi, H.A. Ahmed, J. Douglas, Tim C. Northfield, and Joanne H. Levy

Subjects
Adult, Male, medicine.medical_specialty, Alcoholic liver disease, Pathology, Lymphocyte, Cholangitis, Sclerosing, Intercellular Adhesion Molecule-1, Enzyme-Linked Immunosorbent Assay, Biology, Lymphocyte Activation, Gastroenterology, Primary sclerosing cholangitis, Bile Acids and Salts, Primary biliary cirrhosis, Liver Function Tests, Cholestasis, Internal medicine, medicine, Humans, Liver Diseases, Alcoholic, Aged, Aged, 80 and over, Hepatology, medicine.diagnostic_test, Liver Cirrhosis, Biliary, Receptors, Interleukin-2, Middle Aged, medicine.disease, medicine.anatomical_structure, Liver, Solubility, Alkaline phosphatase, Female, Liver function tests, Biomarkers
Abstract

Intercellular adhesion molecule-1, strongly expressed on the interlobular and proliferating bile ducts in primary biliary cirrhosis, is important in the migration and adhesion of inflammatory cells from the circulation to these structures. A soluble form has been found to be elevated in serum in primary biliary cirrhosis. Our aim was to check on the role of soluble intercellular adhesion molecule-1 in primary biliary cirrhosis with particular reference to its specificity by comparison with other disease control groups and to assess its relationship with stage of disease activity, circulating lymphocyte activation and cholestasis. Soluble intercellular adhesion molecule-1 (enzyme-linked immunosorbent assay) and liver biochemistry were measured in 41 patients with primary biliary cirrhosis, 9 with primary sclerosing cholangitis, 12 with alcoholic liver disease and 17 healthy controls. In subgroups of patients with primary biliary cirrhosis, lymphocyte activation and hepatic bile acid uptake and excretory rates were determined. Soluble intercellular adhesion molecule-1 was significantly higher in all three disease groups. Levels in primary biliary cirrhosis and primary sclerosing cholangitis were similar and significantly higher than alcoholic liver disease. Soluble intercellular adhesion molecule-1 expression was greater in late primary biliary cirrhosis than early disease and correlated with histological progression. Correlations were also found with alkaline phosphatase, gamma-glutamyl transpeptidase and conjugated bilirubin. A trend toward an inverse correlation with hepatic excretory rate was found, but no correlation was detected with circulating lymphocyte interleukin-2 receptor expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Published
1994
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13. Identification of mutations in SLC40A1 that affect ferroportin function and phenotype of human ferroportin iron overload

Author

Timothy M. Cox, Wolfgang Vogel, Andrew C. Douds, Andreas R. Janecke, Ian G. McFarlane, David Halsall, Martin Hermann, Heinz Zoller, Susan E. Davies, William J.H. Griffiths, Armin Finkenstedt, and Roman Mayr

Subjects
Adult, Male, Iron Overload, Biopsy, Iron, Ferroportin, DNA Mutational Analysis, Transfection, Hepcidins, Hepcidin, Humans, Genetic Predisposition to Disease, Cation Transport Proteins, chemistry.chemical_classification, Hepatology, biology, Macrophages, HEK 293 cells, Gastroenterology, Transferrin, Middle Aged, Molecular biology, Phenotype, Magnetic Resonance Imaging, Transport protein, Pedigree, Protein Transport, HEK293 Cells, Biochemistry, chemistry, Liver, Case-Control Studies, Ferritins, Mutation, biology.protein, Intracellular, Antimicrobial Cationic Peptides
Abstract

Background & Aims Patients with ferroportin iron overload due to loss-of-function mutations in SLC40A1 have macrophage iron overload, hyperferritinemia, and normal transferrin saturation. In contrast, hepatocellular iron storage, hyperferritinemia, and increased saturation of transferrin are a distinct clinical presentation of ferroportin iron overload that results from SLC40A1 mutations that confer resistance of ferroportin to hepcidin-mediated inactivation. Methods SLC40A1 was sequenced in patients from 2 independent pedigrees affected by hepatic iron overload unrelated to HFE. Functions of the ferroportin variants were tested in vitro. Results A patient heterozygous for the variant p.W158C in SLC40A1 presented with macrophage iron overload, hyperferritinemia, and normal transferrin saturation. A patient with hepatocellular iron storage, hyperferritinemia, and increased transferrin saturation was heterozygous for p.H507R. Expression of the p.W158C form of ferroportin in 293T cells resulted in defective trafficking to the plasma membrane and reduced iron export activity; the iron export activity of cells that expressed the p.H507R form of ferroportin did not differ from cells that expressed ferroportin without this mutation. The p.H507R of ferroportin localizes normally to the plasma membrane but is resistant to hepcidin-mediated inactivation. Addition of a synthetic peptide derived from ferroportin without these mutations (amino acids 500–518) decreased the inhibitory activity of hepcidin in cells, whereas a peptide from the same region, with p.H507R, had no effect on hepcidin activity. Conclusions The variant p.W158C in SLC40A1 impairs intracellular trafficking of ferroportin, resulting in reduced iron export. The variant p.H507R does not bind hepcidin in vitro and results in apparent hepcidin resistance.

Published
2010

14. Cholangiocarcinoma presenting as hemobilia and recurrent iron-deficiency anemia: a case report

Author

Faisal Tm Basheer, Rajarathnam Mathialagan, Saif S Ahmad, Radhakrishnan Hariraj, Andrew C. Douds, Saad F Idris, Ahmad, Saif [0000-0003-1020-2346], and Apollo - University of Cambridge Repository

Subjects
Liver Cancer, medicine.medical_specialty, Pathology, Anemia, medicine.medical_treatment, lcsh:Medicine, Gastroenterology, digestive system, Clinical, Rare Diseases, Surgical oncology, Internal medicine, Case report, medicine, 2.1 Biological and endogenous factors, In patient, Abnormal liver function, Digestive Diseases - (Gallbladder), Cancer, Curative intent, Medicine(all), business.industry, Liver Disease, lcsh:R, 1103 Clinical Sciences, Hematology, General Medicine, medicine.disease, digestive system diseases, Clinical Medicine and Science, Orphan Drug, Iron-deficiency anemia, Hepatectomy, Digestive Diseases, business
Abstract

Introduction Iron-deficiency anemia is a relatively common presenting feature of several gastrointestinal malignancies. However, cholangiocarcinoma has rarely been reported as an underlying cause. The association of cholangiocarcinoma with the rare clinical finding of hemobilia is also highly unusual. To our knowledge, this is the first case report of cholangiocarcinoma presenting with acute hemobilia and chronic iron-deficiency anemia. Case presentation We report the case of a Caucasian, 84-year-old woman presenting with recurrent, severe iron-deficiency anemia who was eventually diagnosed with intra-hepatic cholangiocarcinoma, following an acute episode of hemobilia. A right hepatectomy was subsequently performed with curative intent, and our patient has now fully recovered. Conclusion This is a rare example of hemobilia and chronic iron-deficiency anemia in association with cholangiocarcinoma. We suggest that a diagnosis of cholangiocarcinoma should be considered in patients who present with iron-deficiency anemia of unknown cause, particularly in the presence of abnormal liver function.

Published
2010

15. Sacral metastasis as a presentation of colonic adenocarcinoma

Author

William T H Gelson, Andrew C. Douds, Martin J Rimmer, and William Landells

Subjects
Male, Poor prognosis, Pathology, medicine.medical_specialty, Sacrum, Adenocarcinoma, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Fatal Outcome, medicine, Grand Round, Humans, 030212 general & internal medicine, Colonic adenocarcinoma, Aged, Spinal Neoplasms, business.industry, General Medicine, medicine.disease, Magnetic Resonance Imaging, digestive system diseases, 030227 psychiatry, Sigmoid Neoplasms, Tomography x ray computed, Bony metastasis, Presentation (obstetrics), business, Tomography, X-Ray Computed
Abstract

Presentation of colonic adenocarcinoma with bony metastasis is rare and associated with a poor prognosis.

Published
2007

16. Is day case liver biopsy underutilised?

Author

C. Finlayson, Andrew C. Douds, J. D. Maxwell, and A.E.A. Joseph

Subjects
Adult, Male, medicine.medical_specialty, Routine practice, Teaching hospital, Biopsy, London, medicine, Humans, Complication rate, Aged, Retrospective Studies, Aged, 80 and over, Medical Audit, medicine.diagnostic_test, business.industry, Liver Diseases, Biopsy, Needle, Gastroenterology, Middle Aged, medicine.disease, Surgery, Specimen Quality, Pneumothorax, Ambulatory Surgical Procedures, Liver, Patient Satisfaction, Liver biopsy, Ambulatory, Chronic Disease, Female, business, Research Article
Abstract

Day case liver biopsies are rarely performed nationally but have been routine practice in selected patients in our hospital since 1989. We have audited our experience of this procedure to compare its safety, and efficacy with inpatient biopsy and assess patient acceptability. Audit data were collected retrospectively on liver biopsies performed at a teaching hospital over 42 months. Acceptability of day case biopsy was assessed by a questionnaire. A total of 182 of 546 biopsies were day cases (33%). The specimen quality was similar in both groups. The overall complication rate did not significantly differ between the two groups (2.7% day case v 3.3% inpatients). There were no deaths or episodes of haemorrhage in the day cases but one patient developed a pneumothorax. Some 91% of those who had a day case biopsy were satisfied with the procedure. Day case liver biopsy is safe, effective, and acceptable in selected patients.

Published
1995

17. Radiotherapy for nasal congestion

Author

Andrew C Douds, David W Young, and Simon Campbell

Subjects
medicine.medical_specialty, business.industry, Stridor, medicine.medical_treatment, General Medicine, respiratory system, Nasal congestion, medicine.disease, respiratory tract diseases, Surgery, FEV1/FVC ratio, Granuloma, medicine, Prednisolone, External beam radiotherapy, Sarcoidosis, medicine.symptom, business, Bilateral hilar lymphadenopathy, medicine.drug
Abstract

Involvement of the larynx and nasopharynx in sarcoidosis is rare. Its course, like other forms of sarcoid, is one of remission and relapse usually responding to high-dose steroids or other forms of immunosuppression. We report a patient with nasopharyngeal and laryngeal sarcoid who failed to respond to immunosuppression but was treated effectively with low-dose radiotherapy. A 39-year-old Afro-Caribbean man presented in November, 1995, with reduced visual acuity. There was no medical or family history of sarcoidosis. Examination confirmed bilateral panuveitis. There were multiple cutaneous nodules on his limbs. Sarcoidosis was confirmed by skin biopsy, a raised serum angiotensin converting enzyme concentration of 109 IU/L, bilateral hilar lymphadenopathy on chest radiography, and characteristic lung function tests (FEV1 3·57 L, FVC 4·08 L, FEV1/FVC 88%, TLCO 4·8 mmol/min per kPa, predicted values FEV1 4·02 L, FVC 4·8 L, FEV1/FVC 84%, TLCO 11·13 mmol/min per kPa). His panuveitis responded to oral prednisolone 60 mg once daily and his lung function tests improved. Prednisolone was reduced to 20 mg once daily over 5 months with no relapse. However, 5 months after presentation, he developed nasal congestion and stridor. Indirect laryngoscopy revealed multiple nasopharyngeal and laryngeal nodules. A biopsy sample showed non-caseating granuloma consistent with sarcoidosis. Despite increasing prednisolone to 60 mg daily and adding cyclosporin, 400 mg once daily for 4 weeks, with satisfactory therapeutic blood concentrations, his nasal congestion and stridor progressively worsened. Cyclosporin was stopped, and on the basis of several successful reports of radiotherapy in steroid refractory neurosarcoid, we decided to treat him with low-dose external beam radiotherapy to his nasopharynx and larynx (20 Gys in 10 fractions over 2 weeks). He had complete remission of his symptoms at 7 weeks and they had not returned 12 months after radiotherapy. His present medication is prednisolone 15 mg once daily. This report is unusual in that sarcoidosis of the nasopharynx and larynx failed to respond to immunosuppressants but was successfully treated by irradiation. We do not advocate the routine use of radiotherapy for the treatment of this form of sarcoidosis on the basis of this single report, but suggest that it may be an alternative treatment in patients with life-threatening disease refractory to conventional immunosuppressant therapy.

Published
1997
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