Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

Andre Franke, Dermot P B McGovern, Jeffrey C. Barrett, Kai Wang, Graham L. Radford-Smith, Tariq Ahmad, Charlie W. Lees, Tobias Balschun, James Lee, Rebecca Roberts, Carl A. Anderson, Joshua C. Bis, Suzanne Bumpstead, David Ellinghaus, Eleonora M. Festen, Michel Georges, Todd Green, Talin Haritunians, Luke Jostins, Anna Latiano & 76 others Christopher G. Mathew, Grant W. Montgomery, Natalie J. Prescott, Soumya Raychaudhuri, Jerome I. Rotter, Philip Schumm, Yashoda Sharma, Lisa A. Simms, Kent D. Taylor, David Whiteman, Cisca Wijmenga, Robert N. Baldassano, Murray Barclay, Theodore M Bayless, Stephan Brand, Carsten Büning, Albert Cohen, Jean Frederick Colombel, Mario Cottone, Laura Stronati, Ted Denson, Martine De Vos, Renata D'Inca, Marla Dubinsky, Cathryn Edwards, Tim Florin, Denis Franchimont, Richard Gearry, Jürgen Glas, Andre Van Gossum, Stephen L. Guthery, Jonas Halfvarson, Hein W. Verspaget, Jean Pierre Hugot, Amir Karban, Debby Laukens, Ian Lawrance, Marc Lemann, Arie Levine, Cecile Libioulle, Edouard Louis, Craig Mowat, William Newman, Juliãn Panés, Anne Phillips, Deborah D. Proctor, Miguel Regueiro, Richard Russell, Paul Rutgeerts, Jeremy Sanderson, Miquel Sans, Frank Seibold, A. Hillary Steinhart, Pieter C F Stokkers, Leif Torkvist, Gerd Kullak-Ublick, David Wilson, Thomas Walters, Stephan R. Targan, Steven R. Brant, John D. Rioux, Mauro D'Amato, Rinse K. Weersma, Subra Kugathasan, Anne M. Griffiths, John C. Mansfield, Severine Vermeire, Richard H. Duerr, Mark S. Silverberg, Jack Satsangi, Stefan Schreiber, Judy H. Cho, Vito Annese, Hakon Hakonarson, Mark J. Daly, Miles Parkes

Research output: Contribution to journalArticle

Abstract

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P <5 × 10 -8). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

Original languageEnglish (US)
Pages (from-to)1118-1125
Number of pages8
JournalNature Genetics
Volume42
Issue number12
DOIs
StatePublished - Dec 2010

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Disease Susceptibility
Crohn Disease
Meta-Analysis
Genome
Genome-Wide Association Study
Computer Simulation
Interleukin-10
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Franke, A., McGovern, D. P. B., Barrett, J. C., Wang, K., Radford-Smith, G. L., Ahmad, T., ... Parkes, M. (2010). Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nature Genetics, 42(12), 1118-1125. https://doi.org/10.1038/ng.717

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. / Franke, Andre; McGovern, Dermot P B; Barrett, Jeffrey C.; Wang, Kai; Radford-Smith, Graham L.; Ahmad, Tariq; Lees, Charlie W.; Balschun, Tobias; Lee, James; Roberts, Rebecca; Anderson, Carl A.; Bis, Joshua C.; Bumpstead, Suzanne; Ellinghaus, David; Festen, Eleonora M.; Georges, Michel; Green, Todd; Haritunians, Talin; Jostins, Luke; Latiano, Anna; Mathew, Christopher G.; Montgomery, Grant W.; Prescott, Natalie J.; Raychaudhuri, Soumya; Rotter, Jerome I.; Schumm, Philip; Sharma, Yashoda; Simms, Lisa A.; Taylor, Kent D.; Whiteman, David; Wijmenga, Cisca; Baldassano, Robert N.; Barclay, Murray; Bayless, Theodore M; Brand, Stephan; Büning, Carsten; Cohen, Albert; Colombel, Jean Frederick; Cottone, Mario; Stronati, Laura; Denson, Ted; De Vos, Martine; D'Inca, Renata; Dubinsky, Marla; Edwards, Cathryn; Florin, Tim; Franchimont, Denis; Gearry, Richard; Glas, Jürgen; Van Gossum, Andre; Guthery, Stephen L.; Halfvarson, Jonas; Verspaget, Hein W.; Hugot, Jean Pierre; Karban, Amir; Laukens, Debby; Lawrance, Ian; Lemann, Marc; Levine, Arie; Libioulle, Cecile; Louis, Edouard; Mowat, Craig; Newman, William; Panés, Juliãn; Phillips, Anne; Proctor, Deborah D.; Regueiro, Miguel; Russell, Richard; Rutgeerts, Paul; Sanderson, Jeremy; Sans, Miquel; Seibold, Frank; Steinhart, A. Hillary; Stokkers, Pieter C F; Torkvist, Leif; Kullak-Ublick, Gerd; Wilson, David; Walters, Thomas; Targan, Stephan R.; Brant, Steven R.; Rioux, John D.; D'Amato, Mauro; Weersma, Rinse K.; Kugathasan, Subra; Griffiths, Anne M.; Mansfield, John C.; Vermeire, Severine; Duerr, Richard H.; Silverberg, Mark S.; Satsangi, Jack; Schreiber, Stefan; Cho, Judy H.; Annese, Vito; Hakonarson, Hakon; Daly, Mark J.; Parkes, Miles.

In: Nature Genetics, Vol. 42, No. 12, 12.2010, p. 1118-1125.

Research output: Contribution to journalArticle

Franke, A, McGovern, DPB, Barrett, JC, Wang, K, Radford-Smith, GL, Ahmad, T, Lees, CW, Balschun, T, Lee, J, Roberts, R, Anderson, CA, Bis, JC, Bumpstead, S, Ellinghaus, D, Festen, EM, Georges, M, Green, T, Haritunians, T, Jostins, L, Latiano, A, Mathew, CG, Montgomery, GW, Prescott, NJ, Raychaudhuri, S, Rotter, JI, Schumm, P, Sharma, Y, Simms, LA, Taylor, KD, Whiteman, D, Wijmenga, C, Baldassano, RN, Barclay, M, Bayless, TM, Brand, S, Büning, C, Cohen, A, Colombel, JF, Cottone, M, Stronati, L, Denson, T, De Vos, M, D'Inca, R, Dubinsky, M, Edwards, C, Florin, T, Franchimont, D, Gearry, R, Glas, J, Van Gossum, A, Guthery, SL, Halfvarson, J, Verspaget, HW, Hugot, JP, Karban, A, Laukens, D, Lawrance, I, Lemann, M, Levine, A, Libioulle, C, Louis, E, Mowat, C, Newman, W, Panés, J, Phillips, A, Proctor, DD, Regueiro, M, Russell, R, Rutgeerts, P, Sanderson, J, Sans, M, Seibold, F, Steinhart, AH, Stokkers, PCF, Torkvist, L, Kullak-Ublick, G, Wilson, D, Walters, T, Targan, SR, Brant, SR, Rioux, JD, D'Amato, M, Weersma, RK, Kugathasan, S, Griffiths, AM, Mansfield, JC, Vermeire, S, Duerr, RH, Silverberg, MS, Satsangi, J, Schreiber, S, Cho, JH, Annese, V, Hakonarson, H, Daly, MJ & Parkes, M 2010, 'Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci', Nature Genetics, vol. 42, no. 12, pp. 1118-1125. https://doi.org/10.1038/ng.717
Franke A, McGovern DPB, Barrett JC, Wang K, Radford-Smith GL, Ahmad T et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nature Genetics. 2010 Dec;42(12):1118-1125. https://doi.org/10.1038/ng.717
Franke, Andre ; McGovern, Dermot P B ; Barrett, Jeffrey C. ; Wang, Kai ; Radford-Smith, Graham L. ; Ahmad, Tariq ; Lees, Charlie W. ; Balschun, Tobias ; Lee, James ; Roberts, Rebecca ; Anderson, Carl A. ; Bis, Joshua C. ; Bumpstead, Suzanne ; Ellinghaus, David ; Festen, Eleonora M. ; Georges, Michel ; Green, Todd ; Haritunians, Talin ; Jostins, Luke ; Latiano, Anna ; Mathew, Christopher G. ; Montgomery, Grant W. ; Prescott, Natalie J. ; Raychaudhuri, Soumya ; Rotter, Jerome I. ; Schumm, Philip ; Sharma, Yashoda ; Simms, Lisa A. ; Taylor, Kent D. ; Whiteman, David ; Wijmenga, Cisca ; Baldassano, Robert N. ; Barclay, Murray ; Bayless, Theodore M ; Brand, Stephan ; Büning, Carsten ; Cohen, Albert ; Colombel, Jean Frederick ; Cottone, Mario ; Stronati, Laura ; Denson, Ted ; De Vos, Martine ; D'Inca, Renata ; Dubinsky, Marla ; Edwards, Cathryn ; Florin, Tim ; Franchimont, Denis ; Gearry, Richard ; Glas, Jürgen ; Van Gossum, Andre ; Guthery, Stephen L. ; Halfvarson, Jonas ; Verspaget, Hein W. ; Hugot, Jean Pierre ; Karban, Amir ; Laukens, Debby ; Lawrance, Ian ; Lemann, Marc ; Levine, Arie ; Libioulle, Cecile ; Louis, Edouard ; Mowat, Craig ; Newman, William ; Panés, Juliãn ; Phillips, Anne ; Proctor, Deborah D. ; Regueiro, Miguel ; Russell, Richard ; Rutgeerts, Paul ; Sanderson, Jeremy ; Sans, Miquel ; Seibold, Frank ; Steinhart, A. Hillary ; Stokkers, Pieter C F ; Torkvist, Leif ; Kullak-Ublick, Gerd ; Wilson, David ; Walters, Thomas ; Targan, Stephan R. ; Brant, Steven R. ; Rioux, John D. ; D'Amato, Mauro ; Weersma, Rinse K. ; Kugathasan, Subra ; Griffiths, Anne M. ; Mansfield, John C. ; Vermeire, Severine ; Duerr, Richard H. ; Silverberg, Mark S. ; Satsangi, Jack ; Schreiber, Stefan ; Cho, Judy H. ; Annese, Vito ; Hakonarson, Hakon ; Daly, Mark J. ; Parkes, Miles. / Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. In: Nature Genetics. 2010 ; Vol. 42, No. 12. pp. 1118-1125.
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AU - Franke, Andre

AU - McGovern, Dermot P B

AU - Barrett, Jeffrey C.

AU - Wang, Kai

AU - Radford-Smith, Graham L.

AU - Ahmad, Tariq

AU - Lees, Charlie W.

AU - Balschun, Tobias

AU - Lee, James

AU - Roberts, Rebecca

AU - Anderson, Carl A.

AU - Bis, Joshua C.

AU - Bumpstead, Suzanne

AU - Ellinghaus, David

AU - Festen, Eleonora M.

AU - Georges, Michel

AU - Green, Todd

AU - Haritunians, Talin

AU - Jostins, Luke

AU - Latiano, Anna

AU - Mathew, Christopher G.

AU - Montgomery, Grant W.

AU - Prescott, Natalie J.

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AU - Rotter, Jerome I.

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AU - Barclay, Murray

AU - Bayless, Theodore M

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AU - Cohen, Albert

AU - Colombel, Jean Frederick

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AU - Halfvarson, Jonas

AU - Verspaget, Hein W.

AU - Hugot, Jean Pierre

AU - Karban, Amir

AU - Laukens, Debby

AU - Lawrance, Ian

AU - Lemann, Marc

AU - Levine, Arie

AU - Libioulle, Cecile

AU - Louis, Edouard

AU - Mowat, Craig

AU - Newman, William

AU - Panés, Juliãn

AU - Phillips, Anne

AU - Proctor, Deborah D.

AU - Regueiro, Miguel

AU - Russell, Richard

AU - Rutgeerts, Paul

AU - Sanderson, Jeremy

AU - Sans, Miquel

AU - Seibold, Frank

AU - Steinhart, A. Hillary

AU - Stokkers, Pieter C F

AU - Torkvist, Leif

AU - Kullak-Ublick, Gerd

AU - Wilson, David

AU - Walters, Thomas

AU - Targan, Stephan R.

AU - Brant, Steven R.

AU - Rioux, John D.

AU - D'Amato, Mauro

AU - Weersma, Rinse K.

AU - Kugathasan, Subra

AU - Griffiths, Anne M.

AU - Mansfield, John C.

AU - Vermeire, Severine

AU - Duerr, Richard H.

AU - Silverberg, Mark S.

AU - Satsangi, Jack

AU - Schreiber, Stefan

AU - Cho, Judy H.

AU - Annese, Vito

AU - Hakonarson, Hakon

AU - Daly, Mark J.

AU - Parkes, Miles

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