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Leonard Baidoo

Other affiliations: Northwestern University
Bio: Leonard Baidoo is an academic researcher from University of Pittsburgh. The author has contributed to research in topics: Inflammatory bowel disease & Crohn's disease. The author has an hindex of 23, co-authored 85 publications receiving 7288 citations. Previous affiliations of Leonard Baidoo include Northwestern University.


Papers
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Journal ArticleDOI
Luke Jostins1, Stephan Ripke2, Rinse K. Weersma3, Richard H. Duerr4, Dermot P.B. McGovern5, Ken Y. Hui6, James Lee7, L. Philip Schumm8, Yashoda Sharma6, Carl A. Anderson1, Jonah Essers9, Mitja Mitrovic3, Kaida Ning6, Isabelle Cleynen10, Emilie Theatre11, Sarah L. Spain12, Soumya Raychaudhuri9, Philippe Goyette13, Zhi Wei14, Clara Abraham6, Jean-Paul Achkar15, Tariq Ahmad16, Leila Amininejad17, Ashwin N. Ananthakrishnan9, Vibeke Andersen18, Jane M. Andrews19, Leonard Baidoo4, Tobias Balschun20, Peter A. Bampton21, Alain Bitton22, Gabrielle Boucher13, Stephan Brand23, Carsten Büning24, Ariella Cohain25, Sven Cichon26, Mauro D'Amato27, Dirk De Jong3, Kathy L Devaney9, Marla Dubinsky5, Cathryn Edwards28, David Ellinghaus20, Lynnette R. Ferguson29, Denis Franchimont17, Karin Fransen3, Richard B. Gearry30, Michel Georges11, Christian Gieger, Jürgen Glas22, Talin Haritunians5, Ailsa Hart31, Christopher J. Hawkey32, Matija Hedl6, Xinli Hu9, Tom H. Karlsen33, Limas Kupčinskas34, Subra Kugathasan35, Anna Latiano36, Debby Laukens37, Ian C. Lawrance38, Charlie W. Lees39, Edouard Louis11, Gillian Mahy40, John C. Mansfield41, Angharad R. Morgan29, Craig Mowat42, William G. Newman43, Orazio Palmieri36, Cyriel Y. Ponsioen44, Uroš Potočnik45, Natalie J. Prescott6, Miguel Regueiro4, Jerome I. Rotter5, Richard K Russell46, Jeremy D. Sanderson47, Miquel Sans, Jack Satsangi39, Stefan Schreiber20, Lisa A. Simms48, Jurgita Sventoraityte34, Stephan R. Targan, Kent D. Taylor5, Mark Tremelling49, Hein W. Verspaget50, Martine De Vos37, Cisca Wijmenga3, David C. Wilson39, Juliane Winkelmann51, Ramnik J. Xavier9, Sebastian Zeissig20, Bin Zhang25, Clarence K. Zhang6, Hongyu Zhao6, Mark S. Silverberg52, Vito Annese, Hakon Hakonarson53, Steven R. Brant54, Graham L. Radford-Smith55, Christopher G. Mathew12, John D. Rioux13, Eric E. Schadt25, Mark J. Daly2, Andre Franke20, Miles Parkes7, Severine Vermeire10, Jeffrey C. Barrett1, Judy H. Cho6 
Wellcome Trust Sanger Institute1, Broad Institute2, University of Groningen3, University of Pittsburgh4, Cedars-Sinai Medical Center5, Yale University6, University of Cambridge7, University of Chicago8, Harvard University9, Katholieke Universiteit Leuven10, University of Liège11, King's College London12, Université de Montréal13, New Jersey Institute of Technology14, Cleveland Clinic15, Peninsula College of Medicine and Dentistry16, Université libre de Bruxelles17, Aarhus University18, University of Adelaide19, University of Kiel20, Flinders University21, McGill University22, Ludwig Maximilian University of Munich23, Charité24, Icahn School of Medicine at Mount Sinai25, University of Bonn26, Karolinska Institutet27, Torbay Hospital28, University of Auckland29, Christchurch Hospital30, Imperial College London31, Queen's University32, University of Oslo33, Lithuanian University of Health Sciences34, Emory University35, Casa Sollievo della Sofferenza36, Ghent University37, University of Western Australia38, University of Edinburgh39, Queensland Health40, Newcastle University41, University of Dundee42, University of Manchester43, University of Amsterdam44, University of Maribor45, Royal Hospital for Sick Children46, Guy's and St Thomas' NHS Foundation Trust47, QIMR Berghofer Medical Research Institute48, Norfolk and Norwich University Hospital49, Leiden University50, Technische Universität München51, University of Toronto52, University of Pennsylvania53, Johns Hopkins University54, University of Queensland55
01 Nov 2012-Nature
TL;DR: A meta-analysis of Crohn’s disease and ulcerative colitis genome-wide association scans is undertaken, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls.
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.

4,094 citations

Journal ArticleDOI
Carl A. Anderson1, Gabrielle Boucher2, Charlie W. Lees3, Andre Franke4, Mauro D'Amato5, Kent D. Taylor6, James Lee7, Philippe Goyette2, Marcin Imielinski8, Anna Latiano9, Caroline Lagacé2, Regan Scott10, Leila Amininejad11, Suzannah Bumpstead1, Leonard Baidoo10, Robert N. Baldassano8, Murray L. Barclay12, Theodore M. Bayless13, Stephan Brand14, Carsten Büning15, Jean-Frederic Colombel16, Lee A. Denson17, Martine De Vos18, Marla Dubinsky6, Cathryn Edwards19, David Ellinghaus4, Rudolf S N Fehrmann20, James A B Floyd1, Timothy H. Florin21, Denis Franchimont11, Lude Franke20, Michel Georges22, Jürgen Glas14, Nicole L. Glazer23, Stephen L. Guthery24, Talin Haritunians6, Nicholas K. Hayward25, Jean-Pierre Hugot26, Gilles Jobin2, Debby Laukens18, Ian C. Lawrance27, Marc Lémann26, Arie Levine28, Cécile Libioulle22, Edouard Louis22, Dermot P.B. McGovern6, Monica Milla, Grant W. Montgomery25, Katherine I. Morley1, Craig Mowat29, Aylwin Ng30, William G. Newman31, Roel A. Ophoff32, Laura Papi33, Orazio Palmieri9, Laurent Peyrin-Biroulet, Julián Panés, Anne M. Phillips29, Natalie J. Prescott34, Deborah D. Proctor35, Rebecca L. Roberts12, Richard K Russell36, Paul Rutgeerts37, Jeremy D. Sanderson38, Miquel Sans39, Philip Schumm40, Frank Seibold41, Yashoda Sharma35, Lisa A. Simms25, Mark Seielstad42, Mark Seielstad43, A. Hillary Steinhart44, Stephan R. Targan6, Leonard H. van den Berg32, Morten H. Vatn45, Hein W. Verspaget46, Thomas D. Walters44, Cisca Wijmenga20, David C. Wilson3, Harm-Jan Westra20, Ramnik J. Xavier30, Zhen Zhen Zhao25, Cyriel Y. Ponsioen47, Vibeke Andersen48, Leif Törkvist5, Maria Gazouli49, Nicholas P. Anagnou49, Tom H. Karlsen45, Limas Kupčinskas50, Jurgita Sventoraityte50, John C. Mansfield51, Subra Kugathasan52, Mark S. Silverberg44, Jonas Halfvarson53, Jerome I. Rotter6, Christopher G. Mathew34, Anne M. Griffiths44, Richard B. Gearry12, Tariq Ahmad, Steven R. Brant13, Mathias Chamaillard54, Jack Satsangi3, Judy H. Cho35, Stefan Schreiber4, Mark J. Daly30, Jeffrey C. Barrett1, Miles Parkes7, Vito Annese9, Hakon Hakonarson55, Graham L. Radford-Smith25, Richard H. Duerr10, Severine Vermeire37, Rinse K. Weersma20, John D. Rioux2 
Wellcome Trust Sanger Institute1, Université de Montréal2, University of Edinburgh3, University of Kiel4, Karolinska Institutet5, Cedars-Sinai Medical Center6, University of Cambridge7, University of Pennsylvania8, Casa Sollievo della Sofferenza9, University of Pittsburgh10, Université libre de Bruxelles11, University of Otago12, Johns Hopkins University13, Ludwig Maximilian University of Munich14, Charité15, Lille University of Science and Technology16, Cincinnati Children's Hospital Medical Center17, Ghent University18, Torbay Hospital19, University of Groningen20, Mater Health Services21, University of Liège22, University of Washington23, University of Utah24, QIMR Berghofer Medical Research Institute25, University of Paris26, University of Western Australia27, Tel Aviv University28, University of Dundee29, Harvard University30, University of Manchester31, Utrecht University32, University of Florence33, King's College London34, Yale University35, Royal Hospital for Sick Children36, Katholieke Universiteit Leuven37, Guy's and St Thomas' NHS Foundation Trust38, University of Barcelona39, University of Chicago40, University of Bern41, Agency for Science, Technology and Research42, University of California, San Francisco43, University of Toronto44, University of Oslo45, Leiden University46, University of Amsterdam47, Aarhus University48, National and Kapodistrian University of Athens49, Lithuanian University of Health Sciences50, Newcastle University51, Emory University52, Örebro University53, French Institute of Health and Medical Research54, Center for Applied Genomics55
TL;DR: A meta-analysis of six ulcerative colitis genome-wide association study datasets found many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1.
Abstract: Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.

1,291 citations

Journal ArticleDOI
TL;DR: In this article, the authors evaluated whether the administration of infliximab after resective intestinal surgery for Crohn's disease reduces postoperative recurrence, and the results showed that the histologic recurrence rate at 1 year was significantly lower in the inflixIMab group (1 of 11 patients; 9.1%) compared with the placebo group (11 of 13 patients; 84.6%) (P =.0006).

523 citations

01 Jan 2009
TL;DR: Administration of infliximab after intestinal resective surgery was effective at preventing endoscopic and histologic recurrence of Crohn's disease.
Abstract: Background & Aims: Crohn’s disease commonly recurs after intestinal resection. We evaluated whether the administration of infliximab after resective intestinal surgery for Crohn’s disease reduces postoperative recurrence. Methods: We randomly assigned 24 patients with Crohn’s disease who had undergone ileocolonic resection to receive intravenous infliximab (5 mg/kg), administered within 4 weeks of surgery and continued for 1 year, or placebo. The primary end point was the proportion of patients with endoscopic recurrence at 1 year. Secondary end points were clinical recurrence and remission and histologic recurrence. Results: The rate of endoscopic recurrence at 1 year was significantly lower in the infliximab group (1 of 11 patients; 9.1%) compared with the placebo group (11 of 13 patients; 84.6%) (P .0006). There was a nonsignificant higher proportion of patients in clinical remission in the infliximab group (8 of 10; 80.0%) compared with the placebo group (7 of 13; 53.8%) (P .38). The histologic recurrence rate at 1 year was significantly lower in the infliximab group (3 of 11 patients; 27.3%) compared with the placebo group (11 of 13 patients; 84.6%) (P .01). The occurrence of adverse events was similar between the placebo and infliximab groups, and none occurred in the immediate postoperative period. Conclusions: Administration of infliximab after intestinal resective surgery was effective at preventing endoscopic and histologic recurrence of Crohn’s disease.

505 citations


Cited by
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Journal ArticleDOI
Stephan Ripke1, Stephan Ripke2, Benjamin M. Neale2, Benjamin M. Neale1  +351 moreInstitutions (102)
24 Jul 2014-Nature
TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

6,809 citations

Journal ArticleDOI
Anshul Kundaje1, Wouter Meuleman1, Wouter Meuleman2, Jason Ernst3, Misha Bilenky4, Angela Yen2, Angela Yen1, Alireza Heravi-Moussavi4, Pouya Kheradpour1, Pouya Kheradpour2, Zhizhuo Zhang2, Zhizhuo Zhang1, Jianrong Wang1, Jianrong Wang2, Michael J. Ziller2, Viren Amin5, John W. Whitaker, Matthew D. Schultz6, Lucas D. Ward1, Lucas D. Ward2, Abhishek Sarkar2, Abhishek Sarkar1, Gerald Quon1, Gerald Quon2, Richard Sandstrom7, Matthew L. Eaton2, Matthew L. Eaton1, Yi-Chieh Wu2, Yi-Chieh Wu1, Andreas R. Pfenning2, Andreas R. Pfenning1, Xinchen Wang1, Xinchen Wang2, Melina Claussnitzer2, Melina Claussnitzer1, Yaping Liu2, Yaping Liu1, Cristian Coarfa5, R. Alan Harris5, Noam Shoresh2, Charles B. Epstein2, Elizabeta Gjoneska1, Elizabeta Gjoneska2, Danny Leung8, Wei Xie8, R. David Hawkins8, Ryan Lister6, Chibo Hong9, Philippe Gascard9, Andrew J. Mungall4, Richard A. Moore4, Eric Chuah4, Angela Tam4, Theresa K. Canfield7, R. Scott Hansen7, Rajinder Kaul7, Peter J. Sabo7, Mukul S. Bansal1, Mukul S. Bansal2, Mukul S. Bansal10, Annaick Carles4, Jesse R. Dixon8, Kai How Farh2, Soheil Feizi2, Soheil Feizi1, Rosa Karlic11, Ah Ram Kim1, Ah Ram Kim2, Ashwinikumar Kulkarni12, Daofeng Li13, Rebecca F. Lowdon13, Ginell Elliott13, Tim R. Mercer14, Shane Neph7, Vitor Onuchic5, Paz Polak2, Paz Polak15, Nisha Rajagopal8, Pradipta R. Ray12, Richard C Sallari1, Richard C Sallari2, Kyle Siebenthall7, Nicholas A Sinnott-Armstrong2, Nicholas A Sinnott-Armstrong1, Michael Stevens13, Robert E. Thurman7, Jie Wu16, Bo Zhang13, Xin Zhou13, Arthur E. Beaudet5, Laurie A. Boyer1, Philip L. De Jager15, Philip L. De Jager2, Peggy J. Farnham17, Susan J. Fisher9, David Haussler18, Steven J.M. Jones19, Steven J.M. Jones4, Wei Li5, Marco A. Marra4, Michael T. McManus9, Shamil R. Sunyaev15, Shamil R. Sunyaev2, James A. Thomson20, Thea D. Tlsty9, Li-Huei Tsai1, Li-Huei Tsai2, Wei Wang, Robert A. Waterland5, Michael Q. Zhang21, Lisa Helbling Chadwick22, Bradley E. Bernstein2, Bradley E. Bernstein15, Bradley E. Bernstein6, Joseph F. Costello9, Joseph R. Ecker11, Martin Hirst4, Alexander Meissner2, Aleksandar Milosavljevic5, Bing Ren8, John A. Stamatoyannopoulos7, Ting Wang13, Manolis Kellis1, Manolis Kellis2 
19 Feb 2015-Nature
TL;DR: It is shown that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

5,037 citations

Journal ArticleDOI
Kristin G. Ardlie, David S. DeLuca, Ayellet V. Segrè, Timothy J. Sullivan, Taylor Young, Ellen Gelfand, Casandra A. Trowbridge, Julian Maller, Taru Tukiainen, Monkol Lek, Lucas D. Ward, Pouya Kheradpour, Benjamin Iriarte, Yan Meng, Cameron D. Palmer, Tõnu Esko, Wendy Winckler, Joel N. Hirschhorn, Manolis Kellis, Daniel G. MacArthur, Gad Getz, Andrey A. Shabalin, Gen Li, Yi-Hui Zhou, Andrew B. Nobel, Ivan Rusyn, Fred A. Wright, Tuuli Lappalainen, Pedro G. Ferreira, Halit Ongen, Manuel A. Rivas, Alexis Battle, Sara Mostafavi, Jean Monlong, Michael Sammeth, Marta Melé, Ferran Reverter, Jakob M. Goldmann, Daphne Koller, Roderic Guigó, Mark I. McCarthy, Emmanouil T. Dermitzakis, Eric R. Gamazon, Hae Kyung Im, Anuar Konkashbaev, Dan L. Nicolae, Nancy J. Cox, Timothée Flutre, Xiaoquan Wen, Matthew Stephens, Jonathan K. Pritchard, Zhidong Tu, Bin Zhang, Tao Huang, Quan Long, Luan Lin, Jialiang Yang, Jun Zhu, Jun Liu, Amanda Brown, Bernadette Mestichelli, Denee Tidwell, Edmund Lo, Mike Salvatore, Saboor Shad, Jeffrey A. Thomas, John T. Lonsdale, Michael T. Moser, Bryan Gillard, Ellen Karasik, Kimberly Ramsey, Christopher Choi, Barbara A. Foster, John Syron, Johnell Fleming, Harold Magazine, Rick Hasz, Gary Walters, Jason Bridge, Mark Miklos, Susan L. Sullivan, Laura Barker, Heather M. Traino, Maghboeba Mosavel, Laura A. Siminoff, Dana R. Valley, Daniel C. Rohrer, Scott D. Jewell, Philip A. Branton, Leslie H. Sobin, Mary Barcus, Liqun Qi, Jeffrey McLean, Pushpa Hariharan, Ki Sung Um, Shenpei Wu, David Tabor, Charles Shive, Anna M. Smith, Stephen A. Buia, Anita H. Undale, Karna Robinson, Nancy Roche, Kimberly M. Valentino, Angela Britton, Robin Burges, Debra Bradbury, Kenneth W. Hambright, John Seleski, Greg E. Korzeniewski, Kenyon Erickson, Yvonne Marcus, Jorge Tejada, Mehran Taherian, Chunrong Lu, Margaret J. Basile, Deborah C. Mash, Simona Volpi, Jeffery P. Struewing, Gary F. Temple, Joy T. Boyer, Deborah Colantuoni, Roger Little, Susan E. Koester, Latarsha J. Carithers, Helen M. Moore, Ping Guan, Carolyn C. Compton, Sherilyn Sawyer, Joanne P. Demchok, Jimmie B. Vaught, Chana A. Rabiner, Nicole C. Lockhart 
08 May 2015-Science
TL;DR: The landscape of gene expression across tissues is described, thousands of tissue-specific and shared regulatory expression quantitative trait loci (eQTL) variants are cataloged, complex network relationships are described, and signals from genome-wide association studies explained by eQTLs are identified.
Abstract: Understanding the functional consequences of genetic variation, and how it affects complex human disease and quantitative traits, remains a critical challenge for biomedicine. We present an analysi...

4,418 citations

01 Feb 2015
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

4,409 citations

Journal ArticleDOI
Luke Jostins1, Stephan Ripke2, Rinse K. Weersma3, Richard H. Duerr4, Dermot P.B. McGovern5, Ken Y. Hui6, James Lee7, L. Philip Schumm8, Yashoda Sharma6, Carl A. Anderson1, Jonah Essers9, Mitja Mitrovic3, Kaida Ning6, Isabelle Cleynen10, Emilie Theatre11, Sarah L. Spain12, Soumya Raychaudhuri9, Philippe Goyette13, Zhi Wei14, Clara Abraham6, Jean-Paul Achkar15, Tariq Ahmad16, Leila Amininejad17, Ashwin N. Ananthakrishnan9, Vibeke Andersen18, Jane M. Andrews19, Leonard Baidoo4, Tobias Balschun20, Peter A. Bampton21, Alain Bitton22, Gabrielle Boucher13, Stephan Brand23, Carsten Büning24, Ariella Cohain25, Sven Cichon26, Mauro D'Amato27, Dirk De Jong3, Kathy L Devaney9, Marla Dubinsky5, Cathryn Edwards28, David Ellinghaus20, Lynnette R. Ferguson29, Denis Franchimont17, Karin Fransen3, Richard B. Gearry30, Michel Georges11, Christian Gieger, Jürgen Glas22, Talin Haritunians5, Ailsa Hart31, Christopher J. Hawkey32, Matija Hedl6, Xinli Hu9, Tom H. Karlsen33, Limas Kupčinskas34, Subra Kugathasan35, Anna Latiano36, Debby Laukens37, Ian C. Lawrance38, Charlie W. Lees39, Edouard Louis11, Gillian Mahy40, John C. Mansfield41, Angharad R. Morgan29, Craig Mowat42, William G. Newman43, Orazio Palmieri36, Cyriel Y. Ponsioen44, Uroš Potočnik45, Natalie J. Prescott6, Miguel Regueiro4, Jerome I. Rotter5, Richard K Russell46, Jeremy D. Sanderson47, Miquel Sans, Jack Satsangi39, Stefan Schreiber20, Lisa A. Simms48, Jurgita Sventoraityte34, Stephan R. Targan, Kent D. Taylor5, Mark Tremelling49, Hein W. Verspaget50, Martine De Vos37, Cisca Wijmenga3, David C. Wilson39, Juliane Winkelmann51, Ramnik J. Xavier9, Sebastian Zeissig20, Bin Zhang25, Clarence K. Zhang6, Hongyu Zhao6, Mark S. Silverberg52, Vito Annese, Hakon Hakonarson53, Steven R. Brant54, Graham L. Radford-Smith55, Christopher G. Mathew12, John D. Rioux13, Eric E. Schadt25, Mark J. Daly2, Andre Franke20, Miles Parkes7, Severine Vermeire10, Jeffrey C. Barrett1, Judy H. Cho6 
Wellcome Trust Sanger Institute1, Broad Institute2, University of Groningen3, University of Pittsburgh4, Cedars-Sinai Medical Center5, Yale University6, University of Cambridge7, University of Chicago8, Harvard University9, Katholieke Universiteit Leuven10, University of Liège11, King's College London12, Université de Montréal13, New Jersey Institute of Technology14, Cleveland Clinic15, Peninsula College of Medicine and Dentistry16, Université libre de Bruxelles17, Aarhus University18, University of Adelaide19, University of Kiel20, Flinders University21, McGill University22, Ludwig Maximilian University of Munich23, Charité24, Icahn School of Medicine at Mount Sinai25, University of Bonn26, Karolinska Institutet27, Torbay Hospital28, University of Auckland29, Christchurch Hospital30, Imperial College London31, Queen's University32, University of Oslo33, Lithuanian University of Health Sciences34, Emory University35, Casa Sollievo della Sofferenza36, Ghent University37, University of Western Australia38, University of Edinburgh39, Queensland Health40, Newcastle University41, University of Dundee42, University of Manchester43, University of Amsterdam44, University of Maribor45, Royal Hospital for Sick Children46, Guy's and St Thomas' NHS Foundation Trust47, QIMR Berghofer Medical Research Institute48, Norfolk and Norwich University Hospital49, Leiden University50, Technische Universität München51, University of Toronto52, University of Pennsylvania53, Johns Hopkins University54, University of Queensland55
01 Nov 2012-Nature
TL;DR: A meta-analysis of Crohn’s disease and ulcerative colitis genome-wide association scans is undertaken, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls.
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.

4,094 citations