Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

Carl A. Anderson; Gabrielle Boucher; Charlie W. Lees; Andre Franke; Mauro D'Amato; Kent D. Taylor; James C. Lee; Philippe Goyette; Marcin Imielinski; Anna Latiano; Caroline Lagacé; Regan Scott; Leila Amininejad; Suzannah Bumpstead; Leonard Baidoo; Robert N. Baldassano; Murray Barclay; Theodore M. Bayless; Stephan Brand; Carsten Büning; Jean Frédéric Colombel; Lee A. Denson; Martine De Vos; Marla Dubinsky; Cathryn Edwards; David Ellinghaus; Rudolf S N Fehrmann; James A B Floyd; Timothy Florin; Denis Franchimont; Lude Franke; Michel Georges; Jürgen Glas; Nicole L. Glazer; Stephen L. Guthery; Talin Haritunians; Nicholas K. Hayward; Jean Pierre Hugot; Gilles Jobin; Debby Laukens; Ian Lawrance; Marc Lémann; Arie Levine; Cecile Libioulle; Edouard Louis; Dermot P. McGovern; Monica Milla; Grant W. Montgomery; Katherine I. Morley; Craig Mowat; Aylwin Ng; William Newman; Roel A. Ophoff; Laura Papi; Orazio Palmieri; Laurent Peyrin-Biroulet; Julián Panés; Anne Phillips; Natalie J. Prescott; Deborah D. Proctor; Rebecca Roberts; Richard Russell; Paul Rutgeerts; Jeremy Sanderson; Miquel Sans; Philip Schumm; Frank Seibold; Yashoda Sharma; Lisa A. Simms; Mark Seielstad; A. Hillary Steinhart; Stephan R. Targan; Leonard H. Van Den Berg; Morten Vatn; Hein Verspaget; Thomas Walters; Cisca Wijmenga; David C. Wilson; Harm Jan Westra; Ramnik J. Xavier; Zhen Z. Zhao; Cyriel Y. Ponsioen; Vibeke Andersen; Leif Torkvist; Maria Gazouli; Nicholas P. Anagnou; Tom H. Karlsen; Limas Kupcinskas; Jurgita Sventoraityte; John C. Mansfield; Subra Kugathasan; Mark S. Silverberg; Jonas Halfvarson; Jerome I. Rotter; Christopher G. Mathew; Anne M. Griffiths; Richard Gearry; Tariq Ahmad; Steven R. Brant; Mathias Chamaillard; Jack Satsangi; Judy H. Cho; Stefan Schreiber; Mark J. Daly; Jeffrey C. Barrett; Miles Parkes; Vito Annese; Hakon Hakonarson; Graham Radford-Smith; Richard H. Duerr; Séverine Vermeire; Rinse K. Weersma; John D. Rioux

doi:10.1038/ng.764

Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

Carl A. Anderson, Gabrielle Boucher, Charlie W. Lees, Andre Franke, Mauro D'Amato, Kent D. Taylor, James C. Lee, Philippe Goyette, Marcin Imielinski, Anna Latiano, Caroline Lagacé, Regan Scott, Leila Amininejad, Suzannah Bumpstead, Leonard Baidoo, Robert N. Baldassano, Murray Barclay, Theodore M. Bayless, Stephan Brand, Carsten BüningJean Frédéric Colombel, Lee A. Denson, Martine De Vos, Marla Dubinsky, Cathryn Edwards, David Ellinghaus, Rudolf S N Fehrmann, James A B Floyd, Timothy Florin, Denis Franchimont, Lude Franke, Michel Georges, Jürgen Glas, Nicole L. Glazer, Stephen L. Guthery, Talin Haritunians, Nicholas K. Hayward, Jean Pierre Hugot, Gilles Jobin, Debby Laukens, Ian Lawrance, Marc Lémann, Arie Levine, Cecile Libioulle, Edouard Louis, Dermot P. McGovern, Monica Milla, Grant W. Montgomery, Katherine I. Morley, Craig Mowat, Aylwin Ng, William Newman, Roel A. Ophoff, Laura Papi, Orazio Palmieri, Laurent Peyrin-Biroulet, Julián Panés, Anne Phillips, Natalie J. Prescott, Deborah D. Proctor, Rebecca Roberts, Richard Russell, Paul Rutgeerts, Jeremy Sanderson, Miquel Sans, Philip Schumm, Frank Seibold, Yashoda Sharma, Lisa A. Simms, Mark Seielstad, A. Hillary Steinhart, Stephan R. Targan, Leonard H. Van Den Berg, Morten Vatn, Hein Verspaget, Thomas Walters, Cisca Wijmenga, David C. Wilson, Harm Jan Westra, Ramnik J. Xavier, Zhen Z. Zhao, Cyriel Y. Ponsioen, Vibeke Andersen, Leif Torkvist, Maria Gazouli, Nicholas P. Anagnou, Tom H. Karlsen, Limas Kupcinskas, Jurgita Sventoraityte, John C. Mansfield, Subra Kugathasan, Mark S. Silverberg, Jonas Halfvarson, Jerome I. Rotter, Christopher G. Mathew, Anne M. Griffiths, Richard Gearry, Tariq Ahmad, Steven R. Brant, Mathias Chamaillard, Jack Satsangi, Judy H. Cho, Stefan Schreiber, Mark J. Daly, Jeffrey C. Barrett, Miles Parkes, Vito Annese, Hakon Hakonarson, Graham Radford-Smith, Richard H. Duerr, Séverine Vermeire, Rinse K. Weersma, John D. Rioux

Medicine, Gastroenterology Division

Research output: Contribution to journal › Review article › peer-review

1130 Scopus citations

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.

Original language	English (US)
Pages (from-to)	246-252
Number of pages	7
Journal	Nature Genetics
Volume	43
Issue number	3
DOIs	https://doi.org/10.1038/ng.764
State	Published - Mar 2011

Funding

In memoriam to Marc L\u00E9mann, who dedicated his life to his patients but died too soon. We thank all the subjects who contributed samples and the physicians and nursing staff who helped with recruitment globally. This study was supported by the German Ministry of Education and Research through the National Genome Research Network, the Popgen biobank and infrastructure support through the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence \u2018Inflammation at Interfaces\u2019. Italian case collections were supported by the Italian Group for IBD and the Italian Society for Paediatric Gastroenterology, Hepatology and Nutrition. We acknowledge funding provided by the Royal Brisbane and Women\u2019s Hospital Foundation, University of Queensland (Ferguson Fellowship), National Health and Medical Research Council, Australia and by the European Community (5th PCRDT). UK case collections were supported by the National Association for Colitis and Crohn\u2019s disease, Wellcome Trust, Medical Research Council UK and Peninsular College of Medicine and Dentistry, Exeter. Activities in Sweden were supported by the Swedish Society of Medicine, the Bengt Ihre Foundation, the Karolinska Institutet, the Swedish National Program for IBD Genetics, the Swedish Organization for IBD, the Swedish Medical Research Council, the Soderbergh Foundation and the Swedish Cancer Foundation. Support for genotyping and genetic data analysis was provided by the Agency for Science Technology and Research (A*STAR), Singapore. We are grateful to the funders and investigators of the Epidemiological Investigation of Rheumatoid Arthritis for providing genotype data from healthy Swedish individuals. The Wellcome Trust Case Control Consortium 2 project was supported by Wellcome Trust grant 083948/Z/07/Z. We also acknowledge the National Institute for Health Research (NIHR) Biomedical Research Centre awards to Guy\u2019s & St. Thomas\u2019 National Health Service (NHS) Trust, King\u2019s College London and to Addenbrooke\u2019s Hospital, University of Cambridge School of Clinical Medicine and to the University of Manchester and Central Manchester Foundation Trust. The NIDDK IBD Genetics Consortium is funded by the following grants: DK062431 (S.R.B.), DK062422 (J.H.C.), DK062420 (R.H.D.), DK062432 (J.D.R.), DK062423 (M.S.S.), DK062413 (D.P.M.), DK076984 (M.J.D.), DK084554 (M.J.D. and D.P.M.) and DK062429 (J.H.C.). J.H.C. is also funded by the Crohn\u2019s and Colitis Foundation of America; S.L.G. by DK069513 and Primary Children\u2019s Medical Center Foundation; and J.D.R. by US National Institutes of Health (NIH)/NIDDK grant DK064869. Cedars-Sinai is supported by National Center for Research Resources (NCRR) grant M01-RR00425, NIH/NIDDK grant P01-DK046763, DK 063491 and Cedars-Sinai Medical Center Inflammatory Bowel Disease Research Funds. E.L., D.F. and S.V. are senior clinical investigators for the Funds for Scientific Research (FWO/FNRS) Belgium. S. Brand was supported by Deutsche Forschungsgemeinschaft (DFG BR 1912/5-1) and Else Kr\u00F6ner-Fresenius-Stiftung (P50/05/EKMS05/62). M.C. was supported by the Programme Hospitalier de Recherche Clinique. C.A.A. is supported by Wellcome Trust grant WT091745/ Z/10/Z. J.C.B. is supported by Wellcome Trust grant WT089120/Z/09/Z. R.K.W. is supported by a clinical fellowship grant (90.700.281) from the Netherlands Organization for Scientific Research (NWO). C.W. is supported by grants from the Celiac Disease Consortium (BSIK03009) and The Netherlands Organization for Scientific Research (NWO, VICI grant 918.66.620). L.H.v.d.B. acknowledges funding from the Prinses Beatrix Fonds, the Adessium Foundation and the Amyotrophic Lateral Sclerosis Association. L.F. received a Horizon Breakthrough grant from the Netherlands Genomics Initiative (93519031) and a VENI grant from NWO (ZonMW grant 916.10.135). R.J.X. and A.N. are funded by DK83756, AI062773, DK043351 and the Helmsley Foundation. Replication genotyping was supported by unrestricted grants from Abbott Laboratories Ltd, Giuliani SpA, Shire PLC and Ferring Pharmaceuticals. We thank the 1958 British Birth Cohort and Banco Nacional deADN, Salamanca, Spain, who supplied control DNA samples. The IBSEN study group and the Norwegian Bone Marrow Donor Registry are acknowledged for contributing the Norwegian patient and control populations. The Cardiovascular Health Study (CHS) research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant numbers U01 HL080295 and R01 HL087652 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. We thank the members of the Quebec IBD Genetic Consortium, in particular A. Bitton, G. Aumais, E.J. Bernard, A. Cohen, C. Deslandres, R. Lahaie, D. Langelier and P. Par\u00E9. Other important contributors are K. Hanigan, N. Huang, P. Webb, D. Whiteman, A. Rutherford, R. Gwilliam, J. Ghori, D. Strachan, W. McCardle, W. Ouwehand, M. Newsky, S. Ehlers, I. Pauselius, K. Holm, C. Sina, M. Regueiro, A. Andriulli and M.C. Renda.

ASJC Scopus subject areas

Genetics

Access to Document

10.1038/ng.764

Cite this

Anderson, C. A., Boucher, G., Lees, C. W., Franke, A., D'Amato, M., Taylor, K. D., Lee, J. C., Goyette, P., Imielinski, M., Latiano, A., Lagacé, C., Scott, R., Amininejad, L., Bumpstead, S., Baidoo, L., Baldassano, R. N., Barclay, M., Bayless, T. M., Brand, S., ... Rioux, J. D. (2011). Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nature Genetics, 43(3), 246-252. https://doi.org/10.1038/ng.764

@article{fe0e2888bec14356b452368ecea5b4dc,

title = "Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47",

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.",

author = "Anderson, {Carl A.} and Gabrielle Boucher and Lees, {Charlie W.} and Andre Franke and Mauro D'Amato and Taylor, {Kent D.} and Lee, {James C.} and Philippe Goyette and Marcin Imielinski and Anna Latiano and Caroline Lagac{\'e} and Regan Scott and Leila Amininejad and Suzannah Bumpstead and Leonard Baidoo and Baldassano, {Robert N.} and Murray Barclay and Bayless, {Theodore M.} and Stephan Brand and Carsten B{\"u}ning and Colombel, {Jean Fr{\'e}d{\'e}ric} and Denson, {Lee A.} and {De Vos}, Martine and Marla Dubinsky and Cathryn Edwards and David Ellinghaus and Fehrmann, {Rudolf S N} and Floyd, {James A B} and Timothy Florin and Denis Franchimont and Lude Franke and Michel Georges and J{\"u}rgen Glas and Glazer, {Nicole L.} and Guthery, {Stephen L.} and Talin Haritunians and Hayward, {Nicholas K.} and Hugot, {Jean Pierre} and Gilles Jobin and Debby Laukens and Ian Lawrance and Marc L{\'e}mann and Arie Levine and Cecile Libioulle and Edouard Louis and McGovern, {Dermot P.} and Monica Milla and Montgomery, {Grant W.} and Morley, {Katherine I.} and Craig Mowat and Aylwin Ng and William Newman and Ophoff, {Roel A.} and Laura Papi and Orazio Palmieri and Laurent Peyrin-Biroulet and Juli{\'a}n Pan{\'e}s and Anne Phillips and Prescott, {Natalie J.} and Proctor, {Deborah D.} and Rebecca Roberts and Richard Russell and Paul Rutgeerts and Jeremy Sanderson and Miquel Sans and Philip Schumm and Frank Seibold and Yashoda Sharma and Simms, {Lisa A.} and Mark Seielstad and Steinhart, {A. Hillary} and Targan, {Stephan R.} and {Van Den Berg}, {Leonard H.} and Morten Vatn and Hein Verspaget and Thomas Walters and Cisca Wijmenga and Wilson, {David C.} and Westra, {Harm Jan} and Xavier, {Ramnik J.} and Zhao, {Zhen Z.} and Ponsioen, {Cyriel Y.} and Vibeke Andersen and Leif Torkvist and Maria Gazouli and Anagnou, {Nicholas P.} and Karlsen, {Tom H.} and Limas Kupcinskas and Jurgita Sventoraityte and Mansfield, {John C.} and Subra Kugathasan and Silverberg, {Mark S.} and Jonas Halfvarson and Rotter, {Jerome I.} and Mathew, {Christopher G.} and Griffiths, {Anne M.} and Richard Gearry and Tariq Ahmad and Brant, {Steven R.} and Mathias Chamaillard and Jack Satsangi and Cho, {Judy H.} and Stefan Schreiber and Daly, {Mark J.} and Barrett, {Jeffrey C.} and Miles Parkes and Vito Annese and Hakon Hakonarson and Graham Radford-Smith and Duerr, {Richard H.} and S{\'e}verine Vermeire and Weersma, {Rinse K.} and Rioux, {John D.}",

note = "Funding Information: Replication genotyping was supported by unrestricted grants from Abbott Laboratories Ltd, Giuliani SpA, Shire PLC and Ferring Pharmaceuticals. We thank the 1958 British Birth Cohort and Banco Nacional deADN, Salamanca, Spain, who supplied control DNA samples. The IBSEN study group and the Norwegian Bone Marrow Donor Registry are acknowledged for contributing the Norwegian patient and control populations. The Cardiovascular Health Study (CHS) research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant numbers U01 HL080295 and R01 HL087652 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. We thank the members of the Quebec IBD Genetic Consortium, in particular A. Bitton, G. Aumais, E.J. Bernard, A. Cohen, C. Deslandres, R. Lahaie, D. Langelier and P. Par{\'e}. Other important contributors are K. Hanigan, N. Huang, P. Webb, D. Whiteman, A. Rutherford, R. Gwilliam, J. Ghori, D. Strachan, W. McCardle, W. Ouwehand, M. Newsky, S. Ehlers, I. Pauselius, K. Holm, C. Sina, M. Regueiro, A. Andriulli and M.C. Renda. Funding Information: In memoriam to Marc L{\'e}mann, who dedicated his life to his patients but died too soon. We thank all the subjects who contributed samples and the physicians and nursing staff who helped with recruitment globally. This study was supported by the German Ministry of Education and Research through the National Genome Research Network, the Popgen biobank and infrastructure support through the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence {\textquoteleft}Inflammation at Interfaces{\textquoteright}. Italian case collections were supported by the Italian Group for IBD and the Italian Society for Paediatric Gastroenterology, Hepatology and Nutrition. We acknowledge funding provided by the Royal Brisbane and Women{\textquoteright}s Hospital Foundation, University of Queensland (Ferguson Fellowship), National Health and Medical Research Council, Australia and by the European Community (5th PCRDT). UK case collections were supported by the National Association for Colitis and Crohn{\textquoteright}s disease, Wellcome Trust, Medical Research Council UK and Peninsular College of Medicine and Dentistry, Exeter. Activities in Sweden were supported by the Swedish Society of Medicine, the Bengt Ihre Foundation, the Karolinska Institutet, the Swedish National Program for IBD Genetics, the Swedish Organization for IBD, the Swedish Medical Research Council, the Soderbergh Foundation and the Swedish Cancer Foundation. Support for genotyping and genetic data analysis was provided by the Agency for Science Technology and Research (A*STAR), Singapore. We are grateful to the funders and investigators of the Epidemiological Investigation of Rheumatoid Arthritis for providing genotype data from healthy Swedish individuals. The Wellcome Trust Case Control Consortium 2 project was supported by Wellcome Trust grant 083948/Z/07/Z. We also acknowledge the National Institute for Health Research (NIHR) Biomedical Research Centre awards to Guy{\textquoteright}s & St. Thomas{\textquoteright} National Health Service (NHS) Trust, King{\textquoteright}s College London and to Addenbrooke{\textquoteright}s Hospital, University of Cambridge School of Clinical Medicine and to the University of Manchester and Central Manchester Foundation Trust. The NIDDK IBD Genetics Consortium is funded by the following grants: DK062431 (S.R.B.), DK062422 (J.H.C.), DK062420 (R.H.D.), DK062432 (J.D.R.), DK062423 (M.S.S.), DK062413 (D.P.M.), DK076984 (M.J.D.), DK084554 (M.J.D. and D.P.M.) and DK062429 (J.H.C.). J.H.C. is also funded by the Crohn{\textquoteright}s and Colitis Foundation of America; S.L.G. by DK069513 and Primary Children{\textquoteright}s Medical Center Foundation; and J.D.R. by US National Institutes of Health (NIH)/NIDDK grant DK064869. Cedars-Sinai is supported by National Center for Research Resources (NCRR) grant M01-RR00425, NIH/NIDDK grant P01-DK046763, DK 063491 and Cedars-Sinai Medical Center Inflammatory Bowel Disease Research Funds. E.L., D.F. and S.V. are senior clinical investigators for the Funds for Scientific Research (FWO/FNRS) Belgium. S. Brand was supported by Deutsche Forschungsgemeinschaft (DFG BR 1912/5-1) and Else Kr{\"o}ner-Fresenius-Stiftung (P50/05/EKMS05/62). M.C. was supported by the Programme Hospitalier de Recherche Clinique. C.A.A. is supported by Wellcome Trust grant WT091745/ Z/10/Z. J.C.B. is supported by Wellcome Trust grant WT089120/Z/09/Z. R.K.W. is supported by a clinical fellowship grant (90.700.281) from the Netherlands Organization for Scientific Research (NWO). C.W. is supported by grants from the Celiac Disease Consortium (BSIK03009) and The Netherlands Organization for Scientific Research (NWO, VICI grant 918.66.620). L.H.v.d.B. acknowledges funding from the Prinses Beatrix Fonds, the Adessium Foundation and the Amyotrophic Lateral Sclerosis Association. L.F. received a Horizon Breakthrough grant from the Netherlands Genomics Initiative (93519031) and a VENI grant from NWO (ZonMW grant 916.10.135). R.J.X. and A.N. are funded by DK83756, AI062773, DK043351 and the Helmsley Foundation.",

year = "2011",

month = mar,

doi = "10.1038/ng.764",

language = "English (US)",

volume = "43",

pages = "246--252",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "3",

}

Anderson, CA, Boucher, G, Lees, CW, Franke, A, D'Amato, M, Taylor, KD, Lee, JC, Goyette, P, Imielinski, M, Latiano, A, Lagacé, C, Scott, R, Amininejad, L, Bumpstead, S, Baidoo, L, Baldassano, RN, Barclay, M, Bayless, TM, Brand, S, Büning, C, Colombel, JF, Denson, LA, De Vos, M, Dubinsky, M, Edwards, C, Ellinghaus, D, Fehrmann, RSN, Floyd, JAB, Florin, T, Franchimont, D, Franke, L, Georges, M, Glas, J, Glazer, NL, Guthery, SL, Haritunians, T, Hayward, NK, Hugot, JP, Jobin, G, Laukens, D, Lawrance, I, Lémann, M, Levine, A, Libioulle, C, Louis, E, McGovern, DP, Milla, M, Montgomery, GW, Morley, KI, Mowat, C, Ng, A, Newman, W, Ophoff, RA, Papi, L, Palmieri, O, Peyrin-Biroulet, L, Panés, J, Phillips, A, Prescott, NJ, Proctor, DD, Roberts, R, Russell, R, Rutgeerts, P, Sanderson, J, Sans, M, Schumm, P, Seibold, F, Sharma, Y, Simms, LA, Seielstad, M, Steinhart, AH, Targan, SR, Van Den Berg, LH, Vatn, M, Verspaget, H, Walters, T, Wijmenga, C, Wilson, DC, Westra, HJ, Xavier, RJ, Zhao, ZZ, Ponsioen, CY, Andersen, V, Torkvist, L, Gazouli, M, Anagnou, NP, Karlsen, TH, Kupcinskas, L, Sventoraityte, J, Mansfield, JC, Kugathasan, S, Silverberg, MS, Halfvarson, J, Rotter, JI, Mathew, CG, Griffiths, AM, Gearry, R, Ahmad, T, Brant, SR, Chamaillard, M, Satsangi, J, Cho, JH, Schreiber, S, Daly, MJ, Barrett, JC, Parkes, M, Annese, V, Hakonarson, H, Radford-Smith, G, Duerr, RH, Vermeire, S, Weersma, RK & Rioux, JD 2011, 'Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47', Nature Genetics, vol. 43, no. 3, pp. 246-252. https://doi.org/10.1038/ng.764

TY - JOUR

T1 - Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

AU - Anderson, Carl A.

AU - Boucher, Gabrielle

AU - Lees, Charlie W.

AU - Franke, Andre

AU - D'Amato, Mauro

AU - Taylor, Kent D.

AU - Lee, James C.

AU - Goyette, Philippe

AU - Imielinski, Marcin

AU - Latiano, Anna

AU - Lagacé, Caroline

AU - Scott, Regan

AU - Amininejad, Leila

AU - Bumpstead, Suzannah

AU - Baidoo, Leonard

AU - Baldassano, Robert N.

AU - Barclay, Murray

AU - Bayless, Theodore M.

AU - Brand, Stephan

AU - Büning, Carsten

AU - Colombel, Jean Frédéric

AU - Denson, Lee A.

AU - De Vos, Martine

AU - Dubinsky, Marla

AU - Edwards, Cathryn

AU - Ellinghaus, David

AU - Fehrmann, Rudolf S N

AU - Floyd, James A B

AU - Florin, Timothy

AU - Franchimont, Denis

AU - Franke, Lude

AU - Georges, Michel

AU - Glas, Jürgen

AU - Glazer, Nicole L.

AU - Guthery, Stephen L.

AU - Haritunians, Talin

AU - Hayward, Nicholas K.

AU - Hugot, Jean Pierre

AU - Jobin, Gilles

AU - Laukens, Debby

AU - Lawrance, Ian

AU - Lémann, Marc

AU - Levine, Arie

AU - Libioulle, Cecile

AU - Louis, Edouard

AU - McGovern, Dermot P.

AU - Milla, Monica

AU - Montgomery, Grant W.

AU - Morley, Katherine I.

AU - Mowat, Craig

AU - Ng, Aylwin

AU - Newman, William

AU - Ophoff, Roel A.

AU - Papi, Laura

AU - Palmieri, Orazio

AU - Peyrin-Biroulet, Laurent

AU - Panés, Julián

AU - Phillips, Anne

AU - Prescott, Natalie J.

AU - Proctor, Deborah D.

AU - Roberts, Rebecca

AU - Russell, Richard

AU - Rutgeerts, Paul

AU - Sanderson, Jeremy

AU - Sans, Miquel

AU - Schumm, Philip

AU - Seibold, Frank

AU - Sharma, Yashoda

AU - Simms, Lisa A.

AU - Seielstad, Mark

AU - Steinhart, A. Hillary

AU - Targan, Stephan R.

AU - Van Den Berg, Leonard H.

AU - Vatn, Morten

AU - Verspaget, Hein

AU - Walters, Thomas

AU - Wijmenga, Cisca

AU - Wilson, David C.

AU - Westra, Harm Jan

AU - Xavier, Ramnik J.

AU - Zhao, Zhen Z.

AU - Ponsioen, Cyriel Y.

AU - Andersen, Vibeke

AU - Torkvist, Leif

AU - Gazouli, Maria

AU - Anagnou, Nicholas P.

AU - Karlsen, Tom H.

AU - Kupcinskas, Limas

AU - Sventoraityte, Jurgita

AU - Mansfield, John C.

AU - Kugathasan, Subra

AU - Silverberg, Mark S.

AU - Halfvarson, Jonas

AU - Rotter, Jerome I.

AU - Mathew, Christopher G.

AU - Griffiths, Anne M.

AU - Gearry, Richard

AU - Ahmad, Tariq

AU - Brant, Steven R.

AU - Chamaillard, Mathias

AU - Satsangi, Jack

AU - Cho, Judy H.

AU - Schreiber, Stefan

AU - Daly, Mark J.

AU - Barrett, Jeffrey C.

AU - Parkes, Miles

AU - Annese, Vito

AU - Hakonarson, Hakon

AU - Radford-Smith, Graham

AU - Duerr, Richard H.

AU - Vermeire, Séverine

AU - Weersma, Rinse K.

AU - Rioux, John D.

N1 - Funding Information: Replication genotyping was supported by unrestricted grants from Abbott Laboratories Ltd, Giuliani SpA, Shire PLC and Ferring Pharmaceuticals. We thank the 1958 British Birth Cohort and Banco Nacional deADN, Salamanca, Spain, who supplied control DNA samples. The IBSEN study group and the Norwegian Bone Marrow Donor Registry are acknowledged for contributing the Norwegian patient and control populations. The Cardiovascular Health Study (CHS) research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant numbers U01 HL080295 and R01 HL087652 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. We thank the members of the Quebec IBD Genetic Consortium, in particular A. Bitton, G. Aumais, E.J. Bernard, A. Cohen, C. Deslandres, R. Lahaie, D. Langelier and P. Paré. Other important contributors are K. Hanigan, N. Huang, P. Webb, D. Whiteman, A. Rutherford, R. Gwilliam, J. Ghori, D. Strachan, W. McCardle, W. Ouwehand, M. Newsky, S. Ehlers, I. Pauselius, K. Holm, C. Sina, M. Regueiro, A. Andriulli and M.C. Renda. Funding Information: In memoriam to Marc Lémann, who dedicated his life to his patients but died too soon. We thank all the subjects who contributed samples and the physicians and nursing staff who helped with recruitment globally. This study was supported by the German Ministry of Education and Research through the National Genome Research Network, the Popgen biobank and infrastructure support through the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence ‘Inflammation at Interfaces’. Italian case collections were supported by the Italian Group for IBD and the Italian Society for Paediatric Gastroenterology, Hepatology and Nutrition. We acknowledge funding provided by the Royal Brisbane and Women’s Hospital Foundation, University of Queensland (Ferguson Fellowship), National Health and Medical Research Council, Australia and by the European Community (5th PCRDT). UK case collections were supported by the National Association for Colitis and Crohn’s disease, Wellcome Trust, Medical Research Council UK and Peninsular College of Medicine and Dentistry, Exeter. Activities in Sweden were supported by the Swedish Society of Medicine, the Bengt Ihre Foundation, the Karolinska Institutet, the Swedish National Program for IBD Genetics, the Swedish Organization for IBD, the Swedish Medical Research Council, the Soderbergh Foundation and the Swedish Cancer Foundation. Support for genotyping and genetic data analysis was provided by the Agency for Science Technology and Research (A*STAR), Singapore. We are grateful to the funders and investigators of the Epidemiological Investigation of Rheumatoid Arthritis for providing genotype data from healthy Swedish individuals. The Wellcome Trust Case Control Consortium 2 project was supported by Wellcome Trust grant 083948/Z/07/Z. We also acknowledge the National Institute for Health Research (NIHR) Biomedical Research Centre awards to Guy’s & St. Thomas’ National Health Service (NHS) Trust, King’s College London and to Addenbrooke’s Hospital, University of Cambridge School of Clinical Medicine and to the University of Manchester and Central Manchester Foundation Trust. The NIDDK IBD Genetics Consortium is funded by the following grants: DK062431 (S.R.B.), DK062422 (J.H.C.), DK062420 (R.H.D.), DK062432 (J.D.R.), DK062423 (M.S.S.), DK062413 (D.P.M.), DK076984 (M.J.D.), DK084554 (M.J.D. and D.P.M.) and DK062429 (J.H.C.). J.H.C. is also funded by the Crohn’s and Colitis Foundation of America; S.L.G. by DK069513 and Primary Children’s Medical Center Foundation; and J.D.R. by US National Institutes of Health (NIH)/NIDDK grant DK064869. Cedars-Sinai is supported by National Center for Research Resources (NCRR) grant M01-RR00425, NIH/NIDDK grant P01-DK046763, DK 063491 and Cedars-Sinai Medical Center Inflammatory Bowel Disease Research Funds. E.L., D.F. and S.V. are senior clinical investigators for the Funds for Scientific Research (FWO/FNRS) Belgium. S. Brand was supported by Deutsche Forschungsgemeinschaft (DFG BR 1912/5-1) and Else Kröner-Fresenius-Stiftung (P50/05/EKMS05/62). M.C. was supported by the Programme Hospitalier de Recherche Clinique. C.A.A. is supported by Wellcome Trust grant WT091745/ Z/10/Z. J.C.B. is supported by Wellcome Trust grant WT089120/Z/09/Z. R.K.W. is supported by a clinical fellowship grant (90.700.281) from the Netherlands Organization for Scientific Research (NWO). C.W. is supported by grants from the Celiac Disease Consortium (BSIK03009) and The Netherlands Organization for Scientific Research (NWO, VICI grant 918.66.620). L.H.v.d.B. acknowledges funding from the Prinses Beatrix Fonds, the Adessium Foundation and the Amyotrophic Lateral Sclerosis Association. L.F. received a Horizon Breakthrough grant from the Netherlands Genomics Initiative (93519031) and a VENI grant from NWO (ZonMW grant 916.10.135). R.J.X. and A.N. are funded by DK83756, AI062773, DK043351 and the Helmsley Foundation.

PY - 2011/3

Y1 - 2011/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79952195585&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952195585&partnerID=8YFLogxK

U2 - 10.1038/ng.764

DO - 10.1038/ng.764

M3 - Review article

C2 - 21297633

AN - SCOPUS:79952195585

SN - 1061-4036

VL - 43

SP - 246

EP - 252

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

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