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; 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

doi:10.1038/ng.717

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 LatianoChristopher 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 (Lead / Corresponding author)

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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 language	English
Pages (from-to)	1118-1125
Number of pages	8
Journal	Nature Genetics
Volume	42
Issue number	12
Early online date	21 Nov 2010
DOIs	https://doi.org/10.1038/ng.717
Publication status	Published - Dec 2010

ASJC Scopus subject areas

Genetics

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Franke, A., McGovern, D. P. B., Barrett, J. C., Wang, K., Radford-Smith, G. L., Ahmad, T., Lees, C. W., Balschun, T., Lee, J., Roberts, R., Anderson, C. A., Bis, J. C., Bumpstead, S., Ellinghaus, D., Festen, E. M., Georges, M., Green, T., Haritunians, T., Jostins, L., ... 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

@article{8be9cbe579a8402e9431aa73b0c99450,

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

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.",

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

year = "2010",

month = dec,

doi = "10.1038/ng.717",

language = "English",

volume = "42",

pages = "1118--1125",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "12",

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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

TY - JOUR

T1 - Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

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.

AU - Raychaudhuri, Soumya

AU - Rotter, Jerome I.

AU - Schumm, Philip

AU - Sharma, Yashoda

AU - Simms, Lisa A.

AU - Taylor, Kent D.

AU - Whiteman, David

AU - Wijmenga, Cisca

AU - Baldassano, Robert N.

AU - Barclay, Murray

AU - Bayless, Theodore M.

AU - Brand, Stephan

AU - Büning, Carsten

AU - Cohen, Albert

AU - Colombel, Jean Frederick

AU - Cottone, Mario

AU - Stronati, Laura

AU - Denson, Ted

AU - De Vos, Martine

AU - D'Inca, Renata

AU - Dubinsky, Marla

AU - Edwards, Cathryn

AU - Florin, Tim

AU - Franchimont, Denis

AU - Gearry, Richard

AU - Glas, Jürgen

AU - Van Gossum, Andre

AU - Guthery, Stephen L.

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

PY - 2010/12

Y1 - 2010/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=78649489009&partnerID=8YFLogxK

U2 - 10.1038/ng.717

DO - 10.1038/ng.717

M3 - Article

AN - SCOPUS:78649489009

SN - 1061-4036

VL - 42

SP - 1118

EP - 1125

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

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

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