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16 results on '"Theatre, Emilie"'

1. HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44+ Natural Killer Cells in Ulcerative Colitis

Author

Akar, Alaa, Flemming, Cornelius, Felix, Flomm, Flosbach, Markus, Jäger, Julia, Jeromin, Niklas, Jung, Johannes, Ohms, Mareike, Reinshagen, Konrad, Rische, Johann, Sagebiel, Adrian, Sandfort, Deborah, Steinert, Fenja, Tomuschat, Christian, Wesche, Jasmin, Shifteh Abedian, Abraham, Clara, Achkar, Jean-Paul, Ahmad, Tariq, Alberts, Rudi, Alizadeh, Behrooz, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Anderson, Carl A., Andrews, Jane M., Annese, Vito, Aumais, Guy, Baidoo, Leonard, Baldassano, Robert N., Bampton, Peter A., Barclay, Murray, Barrett, Jeffrey C., Bethge, Johannes, Bewshea, Claire, Bis, Joshua C., Bitton, Alain, BK, Thelma, Boucher, Gabrielle, Brain, Oliver, Brand, Stephan, Brant, Steven R., Cheon, Jae Hee, Chew, Angela, Cho, Judy H., Cleynen, Isabelle, Cohain, Ariella, Cooney, Rachel, Croft, Anthony, Daly, Mark J., D'Amato, Mauro, Danese, Silvio, Daryani, Naser Ebrahim, Datta, Lisa Wu, Degenhardt, Frauke, Denapiene, Goda, Denson, Lee A., Devaney, Kathy L., Dewit, Olivier, D'Inca, Renata, Drummond, Hazel E., Dubinsky, Marla, Duerr, Richard H., Edwards, Cathryn, Ellinghaus, David, Ellul, Pierre, Esaki, Motohiro, Essers, Jonah, Ferguson, Lynnette R., Festen, Eleonora A., Fleshner, Philip, Florin, Tim, Franchimont, Denis, Franke, Andre, Fuyuno, Yuta, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Goyette, Philippe, Green, Todd, Griffiths, Anne M., Guthery, Stephen L., Hakonarson, Hakon, Halfvarson, Jonas, Hanigan, Katherine, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hayward, Nicholas K., Hedl, Matija, Henderson, Paul, Hold, Georgina L., Hong, Myhunghee, Hu, Xinli, Huang, Hailiang, Hugot, Jean-Pierre, Hui, Ken Y., Imielinski, Marcin, Jazayeri, Omid, Jonaitis, Laimas, Jostins, Luke, Juyal, Garima, Chandra Juyal, Ramesh, Kalla, Rahul, Karlsen, Tom H., Kennedy, Nicholas A., Khan, Mohammed Azam, Kim, Won Ho, Kitazono, Takanari, Kiudelis, Gediminas, Kubo, Michiaki, Kugathasan, Subra, Kupcinskas, Limas, Lamb, Christopher A., de Lange, Katrina M., Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lee, James C., Lees, Charlie W., Leja, Marcis, Lewis, Nina, Van Limbergen, Johan, Lionetti, Paolo, Liu, Jimmy Z., Louis, Edouard, Luo, Yang, Mahy, Gillian, Malekzadeh, Masoud Mohammad, Malekzadeh, Reza, Mansfield, John, Marriott, Suzie, Massey, Dunecan, Mathew, Christopher G., Matsui, Toshiyuki, McGovern, Dermot P.B., van der Meulen, Andrea, Midha, Vandana, Milgrom, Raquel, Mirzaei, Samaneh, Mitrovic, Mitja, Montgomery, Grant W., Mowat, Craig, Müller, Christoph, Newman, William G., Ng, Aylwin, Ng, Siew C., Evelyn Ng, Sok Meng, Nikolaus, Susanna, Ning, Kaida, Nöthen, Markus, Oikonomou, Ioannis, Okou, David, Orchard, Timothy R., Palmieri, Orazio, Parkes, Miles, Phillips, Anne, Ponsioen, Cyriel Y., Potocnik, Urõs, Poustchi, Hossein, Prescott, Natalie J., Proctor, Deborah D., Radford-Smith, Graham, Rahier, Jean- Francois, Regueiro, Miguel, Reinisch, Walter, Rieder, Florian, Rioux, John D., Roberts, Rebecca, Rogler, Gerhard, Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schadt, Eric E., Scharl, Michael, Schembri, John, Schreiber, Stefan, Schumm, L. Philip, Scott, Regan, Seielstad, Mark, Shah, Tejas, Sharma, Yashoda, Silverberg, Mark S., Simmons, Alison, Simms, Lisa A., Singh, Abhey, Skieceviciene, Jurgita, van Sommeren, Suzanne, Song, Kyuyoung, Sood, Ajit, Spain, Sarah L., Steinhart, A. Hillary, Stempak, Joanne M., Stronati, Laura, Sung, Joseph J.Y., Targan, Stephan R., Taylor, Kirstin M., Theatre, Emilie, Torkvist, Leif, Torres, Esther A., Tremelling, Mark, Uhlig, Holm H., Umeno, Junji, Vahedi, Homayon, Vasiliauskas, Eric, Velde, Anje ter, Ventham, Nicholas T., Vermeire, Severine, Verspaget, Hein W., De Vos, Martine, Walters, Thomas, Wang, Kai, Wang, Ming-Hsi, Weersma, Rinse K., Wei, Zhi, Whiteman, David, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Wong, Sunny H., Xavier, Ramnik J., Yamazaki, Keiko, Yang, Suk-Kyun, Ye, Byong Duk, Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhang, Hu, Zhang, Wei, Zhao, Hongyu, Zhao, Zhen Z., Baumdick, Martin E., Niehrs, Annika, Schwerk, Maria, Hinrichs, Ole, Jordan-Paiz, Ana, Padoan, Benedetta, Wegner, Lucy H.M., Schloer, Sebastian, Zecher, Britta F., Malsy, Jakob, Joshi, Vinita R., Illig, Christin, Schröder-Schwarz, Jennifer, Möller, Kimberly J., Martin, Maureen P., Yuki, Yuko, Ozawa, Mikki, Sauter, Jürgen, Schmidt, Alexander H., Perez, Daniel, Giannou, Anastasios D., Carrington, Mary, Davis, Randall S., Schumacher, Udo, Sauter, Guido, Huber, Samuel, Puelles, Victor G., Melling, Nathaniel, Altfeld, Marcus, and Bunders, Madeleine J.

Published
2023
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2. Analysis of Genes Associated With Monogenic Primary Immunodeficiency Identifies Rare Variants in XIAP in Patients With Crohn’s Disease

Author

Amininejad, Leila, Charloteaux, Benoit, Theatre, Emilie, Liefferinckx, Claire, Dmitrieva, Julia, Hayard, Pierre, Muls, Vincianne, Maisin, Jean-Marc, Schapira, Michael, Ghislain, Jean-Michel, Closset, Pierre, Talib, Mehdi, Abramowicz, Marc, Momozawa, Yukihide, Deffontaine, Valerie, Crins, François, Mni, Myriam, Karim, Latifa, Cambisano, Nadine, Ornemese, Sandra, Zucchi, Alessandro, Minsart, Charlotte, Deviere, Jacques, Hugot, Jean-Pierre, De vos, Martine, Louis, Edouard, Vermeire, Severine, Van Gossum, Andre, Coppieters, Wouter, Twizere, Jean-Claude, Georges, Michel, and Franchimont, Denis

Published
2018
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3. Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Author

Jostins, Luke, Ripke, Stephan, Weersma, Rinse K, Duerr, Richard H, McGovern, Dermot P, Hui, Ken Y, Lee, James C, Philip Schumm, L, Sharma, Yashoda, Anderson, Carl A, Essers, Jonah, Mitrovic, Mitja, Ning, Kaida, Cleynen, Isabelle, Theatre, Emilie, Spain, Sarah L, Raychaudhuri, Soumya, Goyette, Philippe, Wei, Zhi, Abraham, Clara, Achkar, Jean-Paul, Ahmad, Tariq, Amininejad, Leila, Ananthakrishnan, Ashwin N, Andersen, Vibeke, Andrews, Jane M, Baidoo, Leonard, Balschun, Tobias, Bampton, Peter A, Bitton, Alain, Boucher, Gabrielle, Brand, Stephan, Büning, Carsten, Cohain, Ariella, Cichon, Sven, D’Amato, Mauro, De Jong, Dirk, Devaney, Kathy L, Dubinsky, Marla, Edwards, Cathryn, Ellinghaus, David, Ferguson, Lynnette R, Franchimont, Denis, Fransen, Karin, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hedl, Matija, Hu, Xinli, Karlsen, Tom H, Kupcinskas, Limas, Kugathasan, Subra, Latiano, Anna, Laukens, Debby, Lawrance, Ian C, Lees, Charlie W, Louis, Edouard, Mahy, Gillian, Mansfield, John, Morgan, Angharad R, Mowat, Craig, Newman, William, Palmieri, Orazio, Ponsioen, Cyriel Y, Potocnik, Uros, Prescott, Natalie J, Regueiro, Miguel, Rotter, Jerome I, Russell, Richard K, Sanderson, Jeremy D, Sans, Miquel, Satsangi, Jack, Schreiber, Stefan, Simms, Lisa A, Sventoraityte, Jurgita, Targan, Stephan R, Taylor, Kent D, Tremelling, Mark, Verspaget, Hein W, De Vos, Martine, Wijmenga, Cisca, Wilson, David C, Winkelmann, Juliane, Xavier, Ramnik J, Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K, Zhao, Hongyu, Silverberg, Mark S, Annese, Vito, Hakonarson, Hakon, Brant, Steven R, Radford-Smith, Graham, Mathew, Christopher G, Rioux, John D, and Schadt, Eric E

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Crohn's Disease, Human Genome, Autoimmune Disease, Inflammatory Bowel Disease, Digestive Diseases, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Colitis, Ulcerative, Crohn Disease, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Haplotypes, Host-Pathogen Interactions, Humans, Inflammatory Bowel Diseases, Mycobacterium, Mycobacterium Infections, Mycobacterium tuberculosis, Phenotype, Polymorphism, Single Nucleotide, Reproducibility of Results, International IBD Genetics Consortium, General Science & Technology
Abstract

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

Published
2012

4. A Method to Exploit the Structure of Genetic Ancestry Space to Enhance Case-Control Studies

Author

Barclay, Murray, Peyrin-Biroulet, Laurent, Chamaillard, Mathias, Colombel, Jean-Frederick, Cottone, Mario, Croft, Anthony, D’Incà, Renata, Halfvarson, Jonas, Hanigan, Katherine, Henderson, Paul, Hugot, Jean-Pierre, Karban, Amir, Kennedy, Nicholas A., Khan, Mohammed Azam, Lémann, Marc, Levine, Arie, Massey, Dunecan, Milla, Monica, Montgomery, Grant W., Ng, Sok Meng Evelyn, Oikonomou, Ioannis, Peeters, Harald, Proctor, Deborah D., Rahier, Jean-Francois, Roberts, Rebecca, Rutgeerts, Paul, Seibold, Frank, Stronati, Laura, Taylor, Kirstin M., Törkvist, Leif, Ublick, Kullak, Van Limbergen, Johan, Van Gossum, Andre, Vatn, Morten H., Zhang, Hu, Zhang, Wei, Andrews, Jane M., Bampton, Peter A., Florin, Timothy H., Gearry, Richard, Krishnaprasad, Krupa, Lawrance, Ian C., Mahy, Gillian, Radford-Smith, Graham, Roberts, Rebecca L., Simms, Lisa A., Amininijad, Leila, Cleynen, Isabelle, Dewit, Olivier, Franchimont, Denis, Georges, Michel, Laukens, Debby, Theatre, Emilie, Van Gossum, André, Vermeire, Severine, Aumais, Guy, Baidoo, Leonard, Barrie, Arthur M., III, Beck, Karen, Bernard, Edmond-Jean, Binion, David G., Bitton, Alain, Brant, Steve R., Cho, Judy H., Cohen, Albert, Croitoru, Kenneth, Daly, Mark J., Datta, Lisa W., Deslandres, Colette, Duerr, Richard H., Dutridge, Debra, Ferguson, John, Fultz, Joann, Goyette, Philippe, Greenberg, Gordon R., Haritunians, Talin, Jobin, Gilles, Katz, Seymour, Lahaie, Raymond G., McGovern, Dermot P., Nelson, Linda, Ng, Sok Meng, Ning, Kaida, Paré, Pierre, Regueiro, Miguel D., Rioux, John D., Ruggiero, Elizabeth, Schumm, L. Philip, Schwartz, Marc, Scott, Regan, Sharma, Yashoda, Silverberg, Mark S., Spears, Denise, Steinhart, A. Hillary, Stempak, Joanne M., Swoger, Jason M., Tsagarelis, Constantina, Zhang, Clarence, Zhao, Hongyu, Aerts, Jan, Ahmad, Tariq, Arbury, Hazel, Attwood, Anthony, Auton, Adam, Ball, Stephen G., Balmforth, Anthony J., Barnes, Chris, Barrett, Jeffrey C., Barroso, Inês, Barton, Anne, Bennett, Amanda J., Bhaskar, Sanjeev, Blaszczyk, Katarzyna, Bowes, John, Brand, Oliver J., Braund, Peter S., Bredin, Francesca, Breen, Gerome, Brown, Morris J., Bruce, Ian N., Bull, Jaswinder, Burren, Oliver S., Burton, John, Byrnes, Jake, Caesar, Sian, Cardin, Niall, Clee, Chris M., Coffey, Alison J., Connell, John M.C., Conrad, Donald F., Cooper, Jason D., Dominiczak, Anna F., Downes, Kate, Drummond, Hazel E., Dudakia, Darshna, Dunham, Andrew, Ebbs, Bernadette, Eccles, Diana, Edkins, Sarah, Edwards, Cathryn, Elliot, Anna, Emery, Paul, Evans, David M., Evans, Gareth, Eyre, Steve, Farmer, Anne, I, Ferrier, Nicol, Flynn, Edward, Forbes, Alistair, Forty, Liz, Franklyn, Jayne A., Frayling, Timothy M., Freathy, Rachel M., Giannoulatou, Eleni, Gibbs, Polly, Gilbert, Paul, Gordon-Smith, Katherine, Gray, Emma, Green, Elaine, Groves, Chris J., Grozeva, Detelina, Gwilliam, Rhian, Hall, Anita, Hammond, Naomi, Hardy, Matt, Harrison, Pile, Hassanali, Neelam, Hebaishi, Husam, Hines, Sarah, Hinks, Anne, Hitman, Graham A., Hocking, Lynne, Holmes, Chris, Howard, Eleanor, Howard, Philip, Howson, Joanna M.M., Hughes, Debbie, Hunt, Sarah, Isaacs, John D., Jain, Mahim, Jewell, Derek P., Johnson, Toby, Jolley, Jennifer D., Jones, Ian R., Jones, Lisa A., Kirov, George, Langford, Cordelia F., Lango-Allen, Hana, Lathrop, G. Mark, Lee, James, Lee, Kate L., Lees, Charlie, Lewis, Kevin, Lindgren, Cecilia M., Maisuria-Armer, Meeta, Maller, Julian, Mansfield, John, Marchini, Jonathan L., Martin, Paul, Massey, Dunecan C.O., McArdle, Wendy L., McGuffin, Peter, McLay, Kirsten E., McVean, Gil, Mentzer, Alex, Mimmack, Michael L., Morgan, Ann E., Morris, Andrew P., Mowat, Craig, Munroe, Patricia B., Myers, Simon, Newman, William, Nimmo, Elaine R., O’Donovan, Michael C., Onipinla, Abiodun, Ovington, Nigel R., Owen, Michael J., Palin, Kimmo, Palotie, Aarno, Parnell, Kirstie, Pearson, Richard, Pernet, David, Perry, John R.B., Phillips, Anne, Plagnol, Vincent, Prescott, Natalie J., Prokopenko, Inga, Quail, Michael A., Rafelt, Suzanne, Rayner, Nigel W., Reid, David M., Renwick, Anthony, Ring, Susan M., Robertson, Neil, Robson, Samuel, Russell, Ellie, St Clair, David, Sambrook, Jennifer G., Sanderson, Jeremy D., Sawcer, Stephen J., Schuilenburg, Helen, Scott, Carol E., Scott, Richard, Seal, Sheila, Shaw-Hawkins, Sue, Shields, Beverley M., Simmonds, Matthew J., Smyth, Debbie J., Somaskantharajah, Elilan, Spanova, Katarina, Steer, Sophia, Stephens, Jonathan, Stevens, Helen E., Stirrups, Kathy, Stone, Millicent A., Strachan, David P., Su, Zhan, Symmons, Deborah P.M., Thompson, John R., Thomson, Wendy, Tobin, Martin D., Travers, Mary E., Turnbull, Clare, Vukcevic, Damjan, Wain, Louise V., Walker, Mark, Walker, Neil M., Wallace, Chris, Warren-Perry, Margaret, Watkins, Nicholas A., Webster, John, Weedon, Michael N., Wilson, Anthony G., Woodburn, Matthew, Wordsworth, B. Paul, Yau, Chris, Young, Allan H., Zeggini, Eleftheria, Brown, Matthew A., Burton, Paul R., Caulfield, Mark J., Compston, Alastair, Farrall, Martin, Gough, Stephen C.L., Hall, Alistair S., Hattersley, Andrew T., Hill, Adrian V.S., Mathew, Christopher G., Pembrey, Marcus, Satsangi, Jack, Stratton, Michael R., Worthington, Jane, Hurles, Matthew E., Duncanson, Audrey, Ouwehand, Willem H., Parkes, Miles, Rahman, Nazneen, Todd, John A., Samani, Nilesh J., Kwiatkowski, Dominic P., McCarthy, Mark I., Craddock, Nick, Deloukas, Panos, Donnelly, Peter, Blackwell, Jenefer M., Bramon, Elvira, Casas, Juan P., Corvin, Aiden, Jankowski, Janusz, Markus, Hugh S., Palmer, Colin N.A., Plomin, Robert, Rautanen, Anna, Trembath, Richard C., Viswanathan, Ananth C., Wood, Nicholas W., Spencer, Chris C.A., Band, Gavin, Bellenguez, Céline, Freeman, Colin, Hellenthal, Garrett, Pirinen, Matti, Strange, Amy, Blackburn, Hannah, Bumpstead, Suzannah J., Dronov, Serge, Gillman, Matthew, Jayakumar, Alagurevathi, McCann, Owen T., Liddle, Jennifer, Potter, Simon C., Ravindrarajah, Radhi, Ricketts, Michelle, Waller, Matthew, Weston, Paul, Widaa, Sara, Whittaker, Pamela, Bodea, Corneliu A., Neale, Benjamin M., Ripke, Stephan, Devlin, Bernie, and Roeder, Kathryn

Published
2016
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5. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

Author

Cleynen, Isabelle, Boucher, Gabrielle, Jostins, Luke, Schumm, L Philip, Zeissig, Sebastian, Ahmad, Tariq, Andersen, Vibeke, Andrews, Jane M, Annese, Vito, Brand, Stephan, Brant, Steven R, Cho, Judy H, Daly, Mark J, Dubinsky, Marla, Duerr, Richard H, Ferguson, Lynnette R, Franke, Andre, Gearry, Richard B, Goyette, Philippe, Hakonarson, Hakon, Halfvarson, Jonas, Hov, Johannes R, Huang, Hailang, Kennedy, Nicholas A, Kupcinskas, Limas, Lawrance, Ian C, Lee, James C, Satsangi, Jack, Schreiber, Stephan, Théâtre, Emilie, van der Meulen-de Jong, Andrea E, Weersma, Rinse K, Wilson, David C, Parkes, Miles, Vermeire, Severine, Rioux, John D, Mansfield, John, Silverberg, Mark S, Radford-Smith, Graham, McGovern, Dermot P B, Barrett, Jeffrey C, and Lees, Charlie W

Published
2016
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8. High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis

Author

Goyette, Philippe, Boucher, Gabrielle, Mallon, Dermot, Ellinghaus, Eva, Jostins, Luke, Huang, Hailiang, Ripke, Stephan, Gusareva, Elena S., Annese, Vito, Hauser, Stephen L., Oksenberg, Jorge R., Thomsen, Ingo, Leslie, Stephen, Daly, Mark J., Van Steen, Kristel, Duerr, Richard H., Barrett, Jeffrey C., Mcgovern, Dermot P. B., Schumm, L. Philip, Traherne, James A., Carrington, Mary N., Kosmoliaptsis, Vasilis, Karlsen, Tom H., Franke, Andre, Rioux, John D., Abraham, Clara, Achkar, Jean Paul, Ahmad, Tariq, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Anderson, Carl A., Andrews, Jane M., Aumais, Guy, Baidoo, Leonard, Baldassano, Robert N., Balschun, Tobias, Bampton, Peter A., Barclay, Murray, Bayless, Theodore M., Bethge, Johannes, Bis, Joshua C., Bitton, Alain, Brand, Stephan, Brant, Steven R., Buning, Carsten, Chew, Angela, Cho, Judy H., Cleynen, Isabelle, Cohain, Ariella, Croft, Anthony, D'Amato, Mauro, Danese, Silvio, De Jong, Dirk, De Vos, Martine, Denapiene, Goda, Denson, Lee A., Devaney, Kathy L., Dewit, Olivier, D'Inca, Renata, Dubinsky, Marla, Edwards, Cathryn, Ellinghaus, David, Essers, Jonah, Ferguson, Lynnette R., Festen, Eleonora A., Fleshner, Philip, Florin, Tim, Franchimont, Denis, Fransen, Karin, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jurgen, Green, Todd, Griffiths, Anne M., Guthery, Stephen L., Hakonarson, Hakon, Halfvarson, Jonas, Hanigan, Katherine, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hayward, Nicholas K., Hedl, Matija, Henderson, Paul, Xinli, Hu, Hui, Ken Y., Imielinski, Marcin, Ippoliti, Andrew, Jonaitis, Laimas, Kennedy, Nicholas A., Khan, Mohammed Azam, Kiudelis, Gediminas, Kugathasan, Subra, Kupcinskas, Limas, Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lee, James C., Lees, Charlie W., Leja, Marcis, Van Limbergen, Johan, Lionetti, Paolo, Liu, Jimmy Z., Louis, Edouard, Mahy, Gillian, Mansfield, John, Massey, Dunecan, Mathew, Christopher G., Milgrom, Raquel, Mitrovic, Mitja, Montgomery, Grant, Mowat, Craig, Newman, Wwilliam, Aylwin, Ng, Siew C., Ng, Evelyn Ng, Sok Meng, Nikolaus, Susanna, Ning, Kaida, Nothen, Markus, Oikonomou, Ioannis, Palmieri, Orazio, Parkes, Miles, Phillips, Anne, Ponsioen, Cyriel Y., Potocnik, Uros, Prescott, Natalie J., Proctor, Deborah D., Radford Smith, Graham, Rahier, Jean Francois, Raychaudhur, Soumya, Regueiro, Miguel, Rieder, Florian, Roberts, Rebecca, Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schadt, Eric E., Schreiber, Stefan, Scott, Regan, Seielstad, Mark, Sharma, Yashoda, Silverberg, Mark S., Simms, Lisa A., Skieceviciene, Jurgita, Spain, Sarah L., Steinhart, A. Hillary, Stempak, Joanne M., Stronati, Laura, Sventoraityte, Jurgita, Targan, Stephan R., Taylor, Kirstin M., Ter Velde, Anje, Theatre, Emilie, Torkvist, Leif, Tremelling, Mark, Van Der Meulen, Andrea, Van Sommeren, Suzanne, Vasiliauskas, Eric, Vermeire, Severine, Verspaget, Hein W., Walters, Thomas, Wwang, Kai, Wwang, Ming Hsi, Wweersma, Rinse K., Wei, Zhi, Whiteman, David, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Xavier, Ramnik J., Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhang, Hu, Zhang, Wwei, Zhao, Hongyu, Zhao, Zhen Z., Gastroenterology and Hepatology, Traherne, James [0000-0002-6003-8559], Kosmoliaptsis, Vasilis [0000-0001-7298-1387], and Apollo - University of Cambridge Repository

Subjects
Heterozygote, Genotype, Genotyping Techniques, Genetic Linkage, Ulcerative, Human leukocyte antigen, Biology, Major histocompatibility complex, Polymorphism, Single Nucleotide, Article, Primary sclerosing cholangitis, Major Histocompatibility Complex, Alleles, Chromosome Mapping, Colitis, Ulcerative, Crohn Disease, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA-DRB1 Chains, Humans, Inflammatory Bowel Diseases, Phenotype, Genetics, medicine, HLA-DR, Polymorphism, Colitis, HLA-DRB1, Crohn's disease, Single Nucleotide, medicine.disease, Ulcerative colitis, digestive system diseases, Immunology, biology.protein
Abstract

Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD.

Published
2015
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9. CCDC88B is required for pathogenesis of inflammatory bowel disease

Author

Fodil, Nassima, primary, Moradin, Neda, additional, Leung, Vicki, additional, Olivier, Jean-Frederic, additional, Radovanovic, Irena, additional, Jeyakumar, Thiviya, additional, Flores Molina, Manuel, additional, McFarquhar, Ashley, additional, Cayrol, Romain, additional, Bozec, Dominique, additional, Shoukry, Naglaa H., additional, Kubo, Michiaki, additional, Dimitrieva, Julia, additional, Louis, Edouard, additional, Theatre, Emilie, additional, Dahan, Stephanie, additional, Momozawa, Yukihide, additional, Georges, Michel, additional, Yeretssian, Garabet, additional, and Gros, Philippe, additional

Published
2017
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10. A Method to Exploit the Structure of Genetic Ancestry Space to Enhance Case-Control Studies

Author

Bodea, Corneliu A., primary, Neale, Benjamin M., additional, Ripke, Stephan, additional, Daly, Mark J., additional, Devlin, Bernie, additional, Roeder, Kathryn, additional, Barclay, Murray, additional, Peyrin-Biroulet, Laurent, additional, Chamaillard, Mathias, additional, Colombel, Jean-Frederick, additional, Cottone, Mario, additional, Croft, Anthony, additional, D’Incà, Renata, additional, Halfvarson, Jonas, additional, Hanigan, Katherine, additional, Henderson, Paul, additional, Hugot, Jean-Pierre, additional, Karban, Amir, additional, Kennedy, Nicholas A., additional, Khan, Mohammed Azam, additional, Lémann, Marc, additional, Levine, Arie, additional, Massey, Dunecan, additional, Milla, Monica, additional, Montgomery, Grant W., additional, Ng, Sok Meng Evelyn, additional, Oikonomou, Ioannis, additional, Peeters, Harald, additional, Proctor, Deborah D., additional, Rahier, Jean-Francois, additional, Roberts, Rebecca, additional, Rutgeerts, Paul, additional, Seibold, Frank, additional, Stronati, Laura, additional, Taylor, Kirstin M., additional, Törkvist, Leif, additional, Ublick, Kullak, additional, Van Limbergen, Johan, additional, Van Gossum, Andre, additional, Vatn, Morten H., additional, Zhang, Hu, additional, Zhang, Wei, additional, Andrews, Jane M., additional, Bampton, Peter A., additional, Florin, Timothy H., additional, Gearry, Richard, additional, Krishnaprasad, Krupa, additional, Lawrance, Ian C., additional, Mahy, Gillian, additional, Radford-Smith, Graham, additional, Roberts, Rebecca L., additional, Simms, Lisa A., additional, Amininijad, Leila, additional, Cleynen, Isabelle, additional, Dewit, Olivier, additional, Franchimont, Denis, additional, Georges, Michel, additional, Laukens, Debby, additional, Theatre, Emilie, additional, Van Gossum, André, additional, Vermeire, Severine, additional, Aumais, Guy, additional, Baidoo, Leonard, additional, Barrie, Arthur M., additional, Beck, Karen, additional, Bernard, Edmond-Jean, additional, Binion, David G., additional, Bitton, Alain, additional, Brant, Steve R., additional, Cho, Judy H., additional, Cohen, Albert, additional, Croitoru, Kenneth, additional, Datta, Lisa W., additional, Deslandres, Colette, additional, Duerr, Richard H., additional, Dutridge, Debra, additional, Ferguson, John, additional, Fultz, Joann, additional, Goyette, Philippe, additional, Greenberg, Gordon R., additional, Haritunians, Talin, additional, Jobin, Gilles, additional, Katz, Seymour, additional, Lahaie, Raymond G., additional, McGovern, Dermot P., additional, Nelson, Linda, additional, Ng, Sok Meng, additional, Ning, Kaida, additional, Paré, Pierre, additional, Regueiro, Miguel D., additional, Rioux, John D., additional, Ruggiero, Elizabeth, additional, Schumm, L. Philip, additional, Schwartz, Marc, additional, Scott, Regan, additional, Sharma, Yashoda, additional, Silverberg, Mark S., additional, Spears, Denise, additional, Steinhart, A. Hillary, additional, Stempak, Joanne M., additional, Swoger, Jason M., additional, Tsagarelis, Constantina, additional, Zhang, Clarence, additional, Zhao, Hongyu, additional, Aerts, Jan, additional, Ahmad, Tariq, additional, Arbury, Hazel, additional, Attwood, Anthony, additional, Auton, Adam, additional, Ball, Stephen G., additional, Balmforth, Anthony J., additional, Barnes, Chris, additional, Barrett, Jeffrey C., additional, Barroso, Inês, additional, Barton, Anne, additional, Bennett, Amanda J., additional, Bhaskar, Sanjeev, additional, Blaszczyk, Katarzyna, additional, Bowes, John, additional, Brand, Oliver J., additional, Braund, Peter S., additional, Bredin, Francesca, additional, Breen, Gerome, additional, Brown, Morris J., additional, Bruce, Ian N., additional, Bull, Jaswinder, additional, Burren, Oliver S., additional, Burton, John, additional, Byrnes, Jake, additional, Caesar, Sian, additional, Cardin, Niall, additional, Clee, Chris M., additional, Coffey, Alison J., additional, Connell, John M.C., additional, Conrad, Donald F., additional, Cooper, Jason D., additional, Dominiczak, Anna F., additional, Downes, Kate, additional, Drummond, Hazel E., additional, Dudakia, Darshna, additional, Dunham, Andrew, additional, Ebbs, Bernadette, additional, Eccles, Diana, additional, Edkins, Sarah, additional, Edwards, Cathryn, additional, Elliot, Anna, additional, Emery, Paul, additional, Evans, David M., additional, Evans, Gareth, additional, Eyre, Steve, additional, Farmer, Anne, additional, Ferrier, Nicol, additional, Flynn, Edward, additional, Forbes, Alistair, additional, Forty, Liz, additional, Franklyn, Jayne A., additional, Frayling, Timothy M., additional, Freathy, Rachel M., additional, Giannoulatou, Eleni, additional, Gibbs, Polly, additional, Gilbert, Paul, additional, Gordon-Smith, Katherine, additional, Gray, Emma, additional, Green, Elaine, additional, Groves, Chris J., additional, Grozeva, Detelina, additional, Gwilliam, Rhian, additional, Hall, Anita, additional, Hammond, Naomi, additional, Hardy, Matt, additional, Harrison, Pile, additional, Hassanali, Neelam, additional, Hebaishi, Husam, additional, Hines, Sarah, additional, Hinks, Anne, additional, Hitman, Graham A., additional, Hocking, Lynne, additional, Holmes, Chris, additional, Howard, Eleanor, additional, Howard, Philip, additional, Howson, Joanna M.M., additional, Hughes, Debbie, additional, Hunt, Sarah, additional, Isaacs, John D., additional, Jain, Mahim, additional, Jewell, Derek P., additional, Johnson, Toby, additional, Jolley, Jennifer D., additional, Jones, Ian R., additional, Jones, Lisa A., additional, Kirov, George, additional, Langford, Cordelia F., additional, Lango-Allen, Hana, additional, Lathrop, G. Mark, additional, Lee, James, additional, Lee, Kate L., additional, Lees, Charlie, additional, Lewis, Kevin, additional, Lindgren, Cecilia M., additional, Maisuria-Armer, Meeta, additional, Maller, Julian, additional, Mansfield, John, additional, Marchini, Jonathan L., additional, Martin, Paul, additional, Massey, Dunecan C.O., additional, McArdle, Wendy L., additional, McGuffin, Peter, additional, McLay, Kirsten E., additional, McVean, Gil, additional, Mentzer, Alex, additional, Mimmack, Michael L., additional, Morgan, Ann E., additional, Morris, Andrew P., additional, Mowat, Craig, additional, Munroe, Patricia B., additional, Myers, Simon, additional, Newman, William, additional, Nimmo, Elaine R., additional, O’Donovan, Michael C., additional, Onipinla, Abiodun, additional, Ovington, Nigel R., additional, Owen, Michael J., additional, Palin, Kimmo, additional, Palotie, Aarno, additional, Parnell, Kirstie, additional, Pearson, Richard, additional, Pernet, David, additional, Perry, John R.B., additional, Phillips, Anne, additional, Plagnol, Vincent, additional, Prescott, Natalie J., additional, Prokopenko, Inga, additional, Quail, Michael A., additional, Rafelt, Suzanne, additional, Rayner, Nigel W., additional, Reid, David M., additional, Renwick, Anthony, additional, Ring, Susan M., additional, Robertson, Neil, additional, Robson, Samuel, additional, Russell, Ellie, additional, St Clair, David, additional, Sambrook, Jennifer G., additional, Sanderson, Jeremy D., additional, Sawcer, Stephen J., additional, Schuilenburg, Helen, additional, Scott, Carol E., additional, Scott, Richard, additional, Seal, Sheila, additional, Shaw-Hawkins, Sue, additional, Shields, Beverley M., additional, Simmonds, Matthew J., additional, Smyth, Debbie J., additional, Somaskantharajah, Elilan, additional, Spanova, Katarina, additional, Steer, Sophia, additional, Stephens, Jonathan, additional, Stevens, Helen E., additional, Stirrups, Kathy, additional, Stone, Millicent A., additional, Strachan, David P., additional, Su, Zhan, additional, Symmons, Deborah P.M., additional, Thompson, John R., additional, Thomson, Wendy, additional, Tobin, Martin D., additional, Travers, Mary E., additional, Turnbull, Clare, additional, Vukcevic, Damjan, additional, Wain, Louise V., additional, Walker, Mark, additional, Walker, Neil M., additional, Wallace, Chris, additional, Warren-Perry, Margaret, additional, Watkins, Nicholas A., additional, Webster, John, additional, Weedon, Michael N., additional, Wilson, Anthony G., additional, Woodburn, Matthew, additional, Wordsworth, B. Paul, additional, Yau, Chris, additional, Young, Allan H., additional, Zeggini, Eleftheria, additional, Brown, Matthew A., additional, Burton, Paul R., additional, Caulfield, Mark J., additional, Compston, Alastair, additional, Farrall, Martin, additional, Gough, Stephen C.L., additional, Hall, Alistair S., additional, Hattersley, Andrew T., additional, Hill, Adrian V.S., additional, Mathew, Christopher G., additional, Pembrey, Marcus, additional, Satsangi, Jack, additional, Stratton, Michael R., additional, Worthington, Jane, additional, Hurles, Matthew E., additional, Duncanson, Audrey, additional, Ouwehand, Willem H., additional, Parkes, Miles, additional, Rahman, Nazneen, additional, Todd, John A., additional, Samani, Nilesh J., additional, Kwiatkowski, Dominic P., additional, McCarthy, Mark I., additional, Craddock, Nick, additional, Deloukas, Panos, additional, Donnelly, Peter, additional, Blackwell, Jenefer M., additional, Bramon, Elvira, additional, Casas, Juan P., additional, Corvin, Aiden, additional, Jankowski, Janusz, additional, Markus, Hugh S., additional, Palmer, Colin N.A., additional, Plomin, Robert, additional, Rautanen, Anna, additional, Trembath, Richard C., additional, Viswanathan, Ananth C., additional, Wood, Nicholas W., additional, Spencer, Chris C.A., additional, Band, Gavin, additional, Bellenguez, Céline, additional, Freeman, Colin, additional, Hellenthal, Garrett, additional, Pirinen, Matti, additional, Strange, Amy, additional, Blackburn, Hannah, additional, Bumpstead, Suzannah J., additional, Dronov, Serge, additional, Gillman, Matthew, additional, Jayakumar, Alagurevathi, additional, McCann, Owen T., additional, Liddle, Jennifer, additional, Potter, Simon C., additional, Ravindrarajah, Radhi, additional, Ricketts, Michelle, additional, Waller, Matthew, additional, Weston, Paul, additional, Widaa, Sara, additional, and Whittaker, Pamela, additional

Published
2016
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11. Dual-Specificity Phosphatase 3 Deficiency or Inhibition Limits Platelet Activation and Arterial Thrombosis

Author

Musumeci, Lucia, Musumeci, Lucia, Kuijpers, Marijke J., Gilio, Karen, Hego, Alexandre, Theatre, Emilie, Maurissen, Lisbeth, Vandereyken, Maud, Diogo, Catia V., Lecut, Christelle, Guilmain, William, Bobkova, Ekaterina V., Eble, Johannes A., Dahl, Russell, Drion, Pierre, Rascon, Justin, Mostofi, Yalda, Yuan, Hongbin, Sergienko, Eduard, Chung, Thomas D. Y., Thiry, Marc, Senis, Yotis, Moutschen, Michel, Mustelin, Tomas, Lancellotti, Patrizio, Heemskerk, Johan W. M., Tautz, Lutz, Oury, Cecile, Rahmouni, Souad, Musumeci, Lucia, Musumeci, Lucia, Kuijpers, Marijke J., Gilio, Karen, Hego, Alexandre, Theatre, Emilie, Maurissen, Lisbeth, Vandereyken, Maud, Diogo, Catia V., Lecut, Christelle, Guilmain, William, Bobkova, Ekaterina V., Eble, Johannes A., Dahl, Russell, Drion, Pierre, Rascon, Justin, Mostofi, Yalda, Yuan, Hongbin, Sergienko, Eduard, Chung, Thomas D. Y., Thiry, Marc, Senis, Yotis, Moutschen, Michel, Mustelin, Tomas, Lancellotti, Patrizio, Heemskerk, Johan W. M., Tautz, Lutz, Oury, Cecile, and Rahmouni, Souad

Abstract

Background-A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. A better understanding of the molecular mechanisms leading to platelet activation is important for the development of improved therapies. Recently, protein tyrosine phosphatases have emerged as critical regulators of platelet function. Methods and Results-This is the first report implicating the dual-specificity phosphatase 3 (DUSP3) in platelet signaling and thrombosis. This phosphatase is highly expressed in human and mouse platelets. Platelets from DUSP3-deficient mice displayed a selective impairment of aggregation and granule secretion mediated by the collagen receptor glycoprotein VI and the C-type lectin-like receptor 2. DUSP3-deficient mice were more resistant to collagen-and epinephrine-induced thromboembolism compared with wild-type mice and showed severely impaired thrombus formation on ferric chloride-induced carotid artery injury. Intriguingly, bleeding times were not altered in DUSP3-deficient mice. At the molecular level, DUSP3 deficiency impaired Syk tyrosine phosphorylation, subsequently reducing phosphorylation of phospholipase C gamma 2 and calcium fluxes. To investigate DUSP3 function in human platelets, a novel small-molecule inhibitor of DUSP3 was developed. This compound specifically inhibited collagen-and C-type lectin-like receptor 2-induced human platelet aggregation, thereby phenocopying the effect of DUSP3 deficiency in murine cells. Conclusions-DUSP3 plays a selective and essential role in collagen-and C-type lectin-like receptor 2-mediated platelet activation and thrombus formation in vivo. Inhibition of DUSP3 may prove therapeutic for arterial thrombosis. This is the first time a protein tyrosine phosphatase, implicated in platelet signaling, has been targeted with a small-molecule drug.

Published
2015

12. Genome-Wide Copy Number Variation Scan Identifies Complement Component C4 as Novel Susceptibility Gene for Crohn's Disease

Author

Cleynen, Isabelle, Louis, Edouard, Franchimont, Denis, De Vos, Martine, van Steen, Kristel, Georges, Michel, Moreau, Yves, Vermeesch, Joris Robert, Vermeire, Séverine, Konings, Peter, Robberecht, Caroline, Laukens, Debby, Amininejad, Leila, Theatre, Emilie, MacHiels, Kathleen, Arijs, Ingrid, Rutgeerts, Paul, Cleynen, Isabelle, Louis, Edouard, Franchimont, Denis, De Vos, Martine, van Steen, Kristel, Georges, Michel, Moreau, Yves, Vermeesch, Joris Robert, Vermeire, Séverine, Konings, Peter, Robberecht, Caroline, Laukens, Debby, Amininejad, Leila, Theatre, Emilie, MacHiels, Kathleen, Arijs, Ingrid, and Rutgeerts, Paul

Abstract

The genetic component of Crohn's disease (CD) is well known, with 140 susceptibility loci identified so far. In addition to single nucleotide polymorphisms typically studied in genome-wide scans, copy number variation is responsible for a large proportion of human genetic variation. Methods: We performed a genome-wide search for copy number variants associated with CD using array comparative genomic hybridization. One of the found regions was validated independently through real-time PCR. Serum levels of the found gene were measured in patients and control subjects. Results: We found copy number differences for the C4S and C4L gene variants of complement component C4 in the central major histocompatibility complex region on chromosome 6p21. Specifically, we saw that CD patients tend to have lower C4L and higher C4S copies than control subjects (P = 5.00 • 10-03 and P = 9.11 × 10-04), which was independent of known associated classical HLA I and II alleles (P = 7.68 × 10-03 and P = 6.29 × 10-03). Although C4 serum levels were not different between patients and control subjects, the relationship between C4 copy number and serum level was different for patients and control subjects with higher copy numbers leading to higher serum concentrations in control subjects, compared with CD patients (P < 0.001). Conclusions: C4 is part of the classical activation pathway of the complement system, which is important for (auto)immunity. Low C4L or high C4S copy number, and corresponding effects on C4 serum level, could lead to an exaggerated response against infections, possibly leading to (auto)immune disease., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2015

13. DUSP3 Genetic Deletion Confers M2-like Macrophage–Dependent Tolerance to Septic Shock

Author

Singh, Pratibha, primary, Dejager, Lien, additional, Amand, Mathieu, additional, Theatre, Emilie, additional, Vandereyken, Maud, additional, Zurashvili, Tinatin, additional, Singh, Maneesh, additional, Mack, Matthias, additional, Timmermans, Steven, additional, Musumeci, Lucia, additional, Dejardin, Emmanuel, additional, Mustelin, Tomas, additional, Van Ginderachter, Jo A., additional, Moutschen, Michel, additional, Oury, Cécile, additional, Libert, Claude, additional, and Rahmouni, Souad, additional

Published
2015
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14. 389 A Candidate Gene Study of Rare Monogenic Disorders With IBD-Like Phenotype Identified Rare Variants in XIAP Gene in a Cohort of Early-Onset IBD Patients

Author

Amininejad, Leila, primary, Charloteaux, Benoit, additional, Theatre, Emilie, additional, Van Cauter, Jacques, additional, Hayard, Pierre, additional, Muls, Vinciane, additional, Maisin, Jean- Marc, additional, Schapira, Michael, additional, Abramowicz, Marc, additional, Mni, Myriam, additional, Karim, Latifa, additional, Cambisano, Nadine, additional, Deviere, Jacques, additional, De Vos, Martine, additional, Louis, Edouard, additional, Vermeire, Severine, additional, Van Gossum, Andre M., additional, Coppieters, Wouter, additional, Georges, Michel, additional, and Franchimont, Denis, additional

Published
2015
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16. Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data

Author

Romagnoni, Alberto, Jégou, Simon, Van Steen, Kristel, Wainrib, Gilles, Hugot, Jean-Pierre, Peyrin-Biroulet, Laurent, Chamaillard, Mathias, Colombel, Jean-Frederick, Cottone, Mario, D’Amato, Mauro, D’Incà, Renata, Halfvarson, Jonas, Henderson, Paul, Karban, Amir, Kennedy, Nicholas A., Khan, Mohammed Azam, Lémann, Marc, Levine, Arie, Massey, Dunecan, Milla, Monica, Ng, Sok Meng Evelyn, Oikonomou, Ioannis, Peeters, Harald, Proctor, Deborah D., Rahier, Jean-Francois, Rutgeerts, Paul, Seibold, Frank, Stronati, Laura, Taylor, Kirstin M., Törkvist, Leif, Ublick, Kullak, Van Limbergen, Johan, Van Gossum, Andre, Vatn, Morten H., Zhang, Hu, Zhang, Wei, Andrews, Jane M., Bampton, Peter A., Barclay, Murray, Florin, Timothy H., Gearry, Richard, Krishnaprasad, Krupa, Lawrance, Ian C., Mahy, Gillian, Montgomery, Grant W., Radford-Smith, Graham, Roberts, Rebecca L., Simms, Lisa A., Hanigan, Katherine, Croft, Anthony, Amininijad, Leila, Cleynen, Isabelle, Dewit, Olivier, Franchimont, Denis, Georges, Michel, Laukens, Debby, Theatre, Emilie, Van Gossum, André, Vermeire, Severine, Aumais, Guy, Baidoo, Leonard, Barrie, Arthur M., Beck, Karen, Bernard, Edmond-Jean, Binion, David G., Bitton, Alain, Brant, Steve R., Cho, Judy H., Cohen, Albert, Croitoru, Kenneth, Daly, Mark J., Datta, Lisa W., Deslandres, Colette, Duerr, Richard H., Dutridge, Debra, Ferguson, John, Fultz, Joann, Goyette, Philippe, Greenberg, Gordon R., Haritunians, Talin, Jobin, Gilles, Katz, Seymour, Lahaie, Raymond G., McGovern, Dermot P., Nelson, Linda, Ng, Sok Meng, Ning, Kaida, Paré, Pierre, Regueiro, Miguel D., Rioux, John D., Ruggiero, Elizabeth, Schumm, L. Philip, Schwartz, Marc, Scott, Regan, Sharma, Yashoda, Silverberg, Mark S., Spears, Denise, Steinhart, A. Hillary, Stempak, Joanne M., Swoger, Jason M., Tsagarelis, Constantina, Zhang, Clarence, Zhao, Hongyu, Aerts, Jan, Ahmad, Tariq, Arbury, Hazel, Attwood, Anthony, Auton, Adam, Ball, Stephen G., Balmforth, Anthony J., Barnes, Chris, Barrett, Jeffrey C., Barroso, Inês, Barton, Anne, Bennett, Amanda J., Bhaskar, Sanjeev, Blaszczyk, Katarzyna, Bowes, John, Brand, Oliver J., Braund, Peter S., Bredin, Francesca, Breen, Gerome, Brown, Morris J., Bruce, Ian N., Bull, Jaswinder, Burren, Oliver S., Burton, John, Byrnes, Jake, Caesar, Sian, Cardin, Niall, Clee, Chris M., Coffey, Alison J., MC Connell, John, Conrad, Donald F., Cooper, Jason D., Dominiczak, Anna F., Downes, Kate, Drummond, Hazel E., Dudakia, Darshna, Dunham, Andrew, Ebbs, Bernadette, Eccles, Diana, Edkins, Sarah, Edwards, Cathryn, Elliot, Anna, Emery, Paul, Evans, David M., Evans, Gareth, Eyre, Steve, Farmer, Anne, Ferrier, I. Nicol, Flynn, Edward, Forbes, Alistair, Forty, Liz, Franklyn, Jayne A., Frayling, Timothy M., Freathy, Rachel M., Giannoulatou, Eleni, Gibbs, Polly, Gilbert, Paul, Gordon-Smith, Katherine, Gray, Emma, Green, Elaine, Groves, Chris J., Grozeva, Detelina, Gwilliam, Rhian, Hall, Anita, Hammond, Naomi, Hardy, Matt, Harrison, Pile, Hassanali, Neelam, Hebaishi, Husam, Hines, Sarah, Hinks, Anne, Hitman, Graham A., Hocking, Lynne, Holmes, Chris, Howard, Eleanor, Howard, Philip, Howson, Joanna M. M., Hughes, Debbie, Hunt, Sarah, Isaacs, John D., Jain, Mahim, Jewell, Derek P., Johnson, Toby, Jolley, Jennifer D., Jones, Ian R., Jones, Lisa A., Kirov, George, Langford, Cordelia F., Lango-Allen, Hana, Lathrop, G. Mark, Lee, James, Lee, Kate L., Lees, Charlie, Lewis, Kevin, Lindgren, Cecilia M., Maisuria-Armer, Meeta, Maller, Julian, Mansfield, John, Marchini, Jonathan L., Martin, Paul, Massey, Dunecan CO, McArdle, Wendy L., McGuffin, Peter, McLay, Kirsten E., McVean, Gil, Mentzer, Alex, Mimmack, Michael L., Morgan, Ann E., Morris, Andrew P., Mowat, Craig, Munroe, Patricia B., Myers, Simon, Newman, William, Nimmo, Elaine R., O’Donovan, Michael C., Onipinla, Abiodun, Ovington, Nigel R., Owen, Michael J., Palin, Kimmo, Palotie, Aarno, Parnell, Kirstie, Pearson, Richard, Pernet, David, Perry, John RB, Phillips, Anne, Plagnol, Vincent, Prescott, Natalie J., Prokopenko, Inga, Quail, Michael A., Rafelt, Suzanne, Rayner, Nigel W., Reid, David M., Renwick, Anthony, Ring, Susan M., Robertson, Neil, Robson, Samuel, Russell, Ellie, Clair, David St, Sambrook, Jennifer G., Sanderson, Jeremy D., Sawcer, Stephen J., Schuilenburg, Helen, Scott, Carol E., Scott, Richard, Seal, Sheila, Shaw-Hawkins, Sue, Shields, Beverley M., Simmonds, Matthew J., Smyth, Debbie J., Somaskantharajah, Elilan, Spanova, Katarina, Steer, Sophia, Stephens, Jonathan, Stevens, Helen E., Stirrups, Kathy, Stone, Millicent A., Strachan, David P., Su, Zhan, Symmons, Deborah P. M., Thompson, John R., Thomson, Wendy, Tobin, Martin D., Travers, Mary E., Turnbull, Clare, Vukcevic, Damjan, Wain, Louise V., Walker, Mark, Walker, Neil M., Wallace, Chris, Warren-Perry, Margaret, Watkins, Nicholas A., Webster, John, Weedon, Michael N., Wilson, Anthony G., Woodburn, Matthew, Wordsworth, B. Paul, Yau, Chris, Young, Allan H., Zeggini, Eleftheria, Brown, Matthew A., Burton, Paul R., Caulfield, Mark J., Compston, Alastair, Farrall, Martin, Gough, Stephen C. L., Hall, Alistair S., Hattersley, Andrew T., Hill, Adrian V. S., Mathew, Christopher G., Pembrey, Marcus, Satsangi, Jack, Stratton, Michael R., Worthington, Jane, Hurles, Matthew E., Duncanson, Audrey, Ouwehand, Willem H., Parkes, Miles, Rahman, Nazneen, Todd, John A., Samani, Nilesh J., Kwiatkowski, Dominic P., McCarthy, Mark I., Craddock, Nick, Deloukas, Panos, Donnelly, Peter, Blackwell, Jenefer M., Bramon, Elvira, Casas, Juan P., Corvin, Aiden, Jankowski, Janusz, Markus, Hugh S., Palmer, Colin NA, Plomin, Robert, Rautanen, Anna, Trembath, Richard C., Viswanathan, Ananth C., Wood, Nicholas W., Spencer, Chris C. A., Band, Gavin, Bellenguez, Céline, Freeman, Colin, Hellenthal, Garrett, Pirinen, Matti, Strange, Amy, Blackburn, Hannah, Bumpstead, Suzannah J., Dronov, Serge, Gillman, Matthew, Jayakumar, Alagurevathi, McCann, Owen T., Liddle, Jennifer, Potter, Simon C., Ravindrarajah, Radhi, Ricketts, Michelle, Waller, Matthew, Weston, Paul, Widaa, Sara, and Whittaker, Pamela

Subjects
692/4020/1503/257/1402, 45, 692/308/2056, 45/43, article, 129, 3. Good health
Abstract

Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.

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