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

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

doi:10.1038/ng.3176

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

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	172-179
Number of pages	8
Journal	Nature Genetics
Volume	47
Issue number	2
DOIs	https://doi.org/10.1038/ng.3176
Publication status	Published - Jan 1 2015

ASJC Scopus subject areas

Genetics

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10.1038/ng.3176

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Goyette, P., Boucher, G., Mallon, D., Ellinghaus, E., Jostins, L., Huang, H., Ripke, S., Gusareva, E. S., Annese, V., Hauser, S. L., Oksenberg, J. R., Thomsen, I., Leslie, S., Daly, M. J., Van Steen, K., Duerr, R. H., Barrett, J. C., McGovern, D. P. B., Schumm, L. P., ... Zhao, Z. Z. (2015). 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. Nature Genetics, 47(2), 172-179. https://doi.org/10.1038/ng.3176

Goyette, P, Boucher, G, Mallon, D, Ellinghaus, E, Jostins, L, Huang, H, Ripke, S, Gusareva, ES, Annese, V, Hauser, SL, Oksenberg, JR, Thomsen, I, Leslie, S, Daly, MJ, Van Steen, K, Duerr, RH, Barrett, JC, McGovern, DPB, Schumm, LP, Traherne, JA, Carrington, MN, Kosmoliaptsis, V, Karlsen, TH, Franke, A, Rioux, JD, Abraham, C, Achkar, JP, Ahmad, T, Amininejad, L, Ananthakrishnan, AN, Andersen, V, Anderson, CA, Andrews, JM, Aumais, G, Baidoo, L, Baldassano, RN, Balschun, T, Bampton, PA, Barclay, M, Bayless, TM, Bethge, J, Bis, JC, Bitton, A, Brand, S, Brant, SR, Buning, C, Chew, A, Cho, JH, Cleynen, I, Cohain, A, Croft, A, D'Amato, M, Danese, S, De Jong, D, De Vos, M, Denapiene, G, Denson, LA, Devaney, KL, Dewit, O, D'Inca, R, Dubinsky, M, Edwards, C, Ellinghaus, D, Essers, J, Ferguson, LR, Festen, EA, Fleshner, P, Florin, T, Franchimont, D, Fransen, K, Gearry, R, Georges, M, Gieger, C, Glas, J, Green, T, Griffiths, AM, Guthery, SL, Hakonarson, H, Halfvarson, J, Hanigan, K, Haritunians, T, Hart, A, Hawkey, C, Hayward, NK, Hedl, M, Henderson, P, Hu, X, Hui, KY, Imielinski, M, Ippoliti, A, Jonaitis, L, Kennedy, NA, Khan, MA, Kiudelis, G, Kugathasan, S, Kupcinskas, L, Latiano, A, Laukens, D, Lawrance, IC, Lee, JC, Lees, CW, Leja, M, Van Limbergen, J, Lionetti, P, Liu, JZ, Louis, E, Mahy, G, Mansfield, J, Massey, D, Mathew, CG, Milgrom, R, Mitrovic, M, Montgomery, G, Mowat, C, Newman, W, Ng, A, Ng, SC, Evelyn Ng, SM, Nikolaus, S, Ning, K, Nothen, M, Oikonomou, I, Palmieri, O, Parkes, M, Phillips, A, Ponsioen, CY, Potocnik, U, Prescott, NJ, Proctor, DD, Radford-Smith, G, Rahier, JF, Raychaudhur, S, Regueiro, M, Rieder, F, Roberts, R, Russell, RK, Sanderson, JD, Sans, M, Satsangi, J, Schadt, EE, Schreiber, S, Schumm, LP, Scott, R, Seielstad, M, Sharma, Y, Silverberg, MS, Simms, LA, Skieceviciene, J, Spain, SL, Steinhart, AH, Stempak, JM, Stronati, L, Sventoraityte, J, Targan, SR, Taylor, KM, Ter Velde, A, Theatre, E, Torkvist, L, Tremelling, M, Van Der Meulen, A, Van Sommeren, S, Vasiliauskas, E, Vermeire, S, Verspaget, HW, Walters, T, Wwang, K, Wwang, MH, Wweersma, RK, Wei, Z, Whiteman, D, Wijmenga, C, Wilson, DC, Winkelmann, J, Xavier, RJ, Zeissig, S, Zhang, B, Zhang, CK, Zhang, H, Zhang, W, Zhao, H & Zhao, ZZ 2015, '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', Nature Genetics, vol. 47, no. 2, pp. 172-179. https://doi.org/10.1038/ng.3176

@article{3639377e575946bbaf2d4644eddb325a,

title = "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",

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.",

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

year = "2015",

month = jan,

day = "1",

doi = "10.1038/ng.3176",

language = "English",

volume = "47",

pages = "172--179",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "2",

}

TY - JOUR

T1 - High-density mapping of the MHC identifies a shared role for HLA-DRB1∗01

T2 - 03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis

AU - Goyette, Philippe

AU - Boucher, Gabrielle

AU - Mallon, Dermot

AU - Ellinghaus, Eva

AU - Jostins, Luke

AU - Huang, Hailiang

AU - Ripke, Stephan

AU - Gusareva, Elena S.

AU - Annese, Vito

AU - Hauser, Stephen L.

AU - Oksenberg, Jorge R.

AU - Thomsen, Ingo

AU - Leslie, Stephen

AU - Daly, Mark J.

AU - Van Steen, Kristel

AU - Duerr, Richard H.

AU - Barrett, Jeffrey C.

AU - McGovern, Dermot P B

AU - Schumm, L. Philip

AU - Traherne, James A.

AU - Carrington, Mary N.

AU - Kosmoliaptsis, Vasilis

AU - Karlsen, Tom H.

AU - Franke, Andre

AU - Rioux, John D.

AU - Abraham, Clara

AU - Achkar, Jean Paul

AU - Ahmad, Tariq

AU - Amininejad, Leila

AU - Ananthakrishnan, Ashwin N.

AU - Andersen, Vibeke

AU - Anderson, Carl A.

AU - Andrews, Jane M.

AU - Aumais, Guy

AU - Baidoo, Leonard

AU - Baldassano, Robert N.

AU - Balschun, Tobias

AU - Bampton, Peter A.

AU - Barclay, Murray

AU - Bayless, Theodore M.

AU - Bethge, Johannes

AU - Bis, Joshua C.

AU - Bitton, Alain

AU - Brand, Stephan

AU - Brant, Steven R.

AU - Buning, Carsten

AU - Chew, Angela

AU - Cho, Judy H.

AU - Cleynen, Isabelle

AU - Cohain, Ariella

AU - Croft, Anthony

AU - D'Amato, Mauro

AU - Danese, Silvio

AU - De Jong, Dirk

AU - De Vos, Martine

AU - Denapiene, Goda

AU - Denson, Lee A.

AU - Devaney, Kathy L.

AU - Dewit, Olivier

AU - D'Inca, Renata

AU - Dubinsky, Marla

AU - Edwards, Cathryn

AU - Ellinghaus, David

AU - Essers, Jonah

AU - Ferguson, Lynnette R.

AU - Festen, Eleonora A.

AU - Fleshner, Philip

AU - Florin, Tim

AU - Franchimont, Denis

AU - Fransen, Karin

AU - Gearry, Richard

AU - Georges, Michel

AU - Gieger, Christian

AU - Glas, Jurgen

AU - Green, Todd

AU - Griffiths, Anne M.

AU - Guthery, Stephen L.

AU - Hakonarson, Hakon

AU - Halfvarson, Jonas

AU - Hanigan, Katherine

AU - Haritunians, Talin

AU - Hart, Ailsa

AU - Hawkey, Chris

AU - Hayward, Nicholas K.

AU - Hedl, Matija

AU - Henderson, Paul

AU - Hu, Xinli

AU - Hui, Ken Y.

AU - Imielinski, Marcin

AU - Ippoliti, Andrew

AU - Jonaitis, Laimas

AU - Kennedy, Nicholas A.

AU - Khan, Mohammed Azam

AU - Kiudelis, Gediminas

AU - Kugathasan, Subra

AU - Kupcinskas, Limas

AU - Latiano, Anna

AU - Laukens, Debby

AU - Lawrance, Ian C.

AU - Lee, James C.

AU - Lees, Charlie W.

AU - Leja, Marcis

AU - Van Limbergen, Johan

AU - Lionetti, Paolo

AU - Liu, Jimmy Z.

AU - Louis, Edouard

AU - Mahy, Gillian

AU - Mansfield, John

AU - Massey, Dunecan

AU - Mathew, Christopher G.

AU - Milgrom, Raquel

AU - Mitrovic, Mitja

AU - Montgomery, Grant

AU - Mowat, Craig

AU - Newman, Wwilliam

AU - Ng, Aylwin

AU - Ng, Siew C.

AU - Evelyn Ng, Sok Meng

AU - Nikolaus, Susanna

AU - Ning, Kaida

AU - Nothen, Markus

AU - Oikonomou, Ioannis

AU - Palmieri, Orazio

AU - Parkes, Miles

AU - Phillips, Anne

AU - Ponsioen, Cyriel Y.

AU - Potocnik, Uros

AU - Prescott, Natalie J.

AU - Proctor, Deborah D.

AU - Radford-Smith, Graham

AU - Rahier, Jean Francois

AU - Raychaudhur, Soumya

AU - Regueiro, Miguel

AU - Rieder, Florian

AU - Roberts, Rebecca

AU - Russell, Richard K.

AU - Sanderson, Jeremy D.

AU - Sans, Miquel

AU - Satsangi, Jack

AU - Schadt, Eric E.

AU - Schreiber, Stefan

AU - Schumm, L. Philip

AU - Scott, Regan

AU - Seielstad, Mark

AU - Sharma, Yashoda

AU - Silverberg, Mark S.

AU - Simms, Lisa A.

AU - Skieceviciene, Jurgita

AU - Spain, Sarah L.

AU - Steinhart, A. Hillary

AU - Stempak, Joanne M.

AU - Stronati, Laura

AU - Sventoraityte, Jurgita

AU - Targan, Stephan R.

AU - Taylor, Kirstin M.

AU - Ter Velde, Anje

AU - Theatre, Emilie

AU - Torkvist, Leif

AU - Tremelling, Mark

AU - Van Der Meulen, Andrea

AU - Van Sommeren, Suzanne

AU - Vasiliauskas, Eric

AU - Vermeire, Severine

AU - Verspaget, Hein W.

AU - Walters, Thomas

AU - Wwang, Kai

AU - Wwang, Ming Hsi

AU - Wweersma, Rinse K.

AU - Wei, Zhi

AU - Whiteman, David

AU - Wijmenga, Cisca

AU - Wilson, David C.

AU - Winkelmann, Juliane

AU - Xavier, Ramnik J.

AU - Zeissig, Sebastian

AU - Zhang, Bin

AU - Zhang, Clarence K.

AU - Zhang, Hu

AU - Zhang, Wwei

AU - Zhao, Hongyu

AU - Zhao, Zhen Z.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

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U2 - 10.1038/ng.3176

DO - 10.1038/ng.3176

M3 - Article

C2 - 25559196

AN - SCOPUS:84928612813

SN - 1061-4036

VL - 47

SP - 172

EP - 179

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

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

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