Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region

Jeffrey C. Barrett; James C. Lee; Charles W. Lees; Natalie J. Prescott; Carl A. Anderson; Anne Phillips; Emma Wesley; Kirstie Parnell; Hu Zhang; Hazel Drummond; Elaine R. Nimmo; Dunecan Massey; Kasia Blaszczyk; Timothy Elliott; Lynn Cotterill; Helen Dallal; Alan J. Lobo; Craig Mowat; Jeremy D. Sanderson; Derek P. Jewell; William G. Newman; Cathryn Edwards; Tariq Ahmad; John C. Mansfield; Jack Satsangi; Miles Parkes; Christopher G. Mathew; Peter Donnelly; Leena Peltonen; Jenefer M. Blackwell; Elvira Bramon; Matthew A. Brown; Juan P. Casas; Aiden Corvin; Nicholas Craddock; Panos Deloukas; Audrey Duncanson; Janusz Jankowski; Hugh S. Markus; Mark I. McCarthy; Colin N. A. Palmer; Robert Plomin; Anna Rautanen; Stephen J. Sawcer; Nilesh Samani; Richard C. Trembath; Ananth C. Viswanathan; Nicholas Wood; Chris C. A. Spencer; Celine Bellenguez; Daniel Davison; Colin Freeman; Amy Strange; Cordelia Langford; Sarah E. Hunt; Sarah Edkins; Rhian Gwilliam; Hannah Blackburn; Suzannah J. Bumpstead; Serge Dronov; Matthew Gillman; Emma Gray; Naomi Hammond; Alagurevathi Jayakumar; Owen T. McCann; Jennifer Liddle; Marc L. Perez; Simon C. Potter; Radhi Ravindrarajah; Michelle Ricketts; Matthew Waller; Paul Weston; Sara Widaa; Pamela Whittaker; Antony P. Attwood; Jonathan Stephens; Jennifer Sambrook; Willem H. Ouwehand; Wendy L. McArdle; Susan M. Ring; David P. Strachan

doi:10.1038/ng.483

Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region

Jeffrey C. Barrett, James C. Lee, Charles W. Lees, Natalie J. Prescott, Carl A. Anderson, Anne Phillips, Emma Wesley, Kirstie Parnell, Hu Zhang, Hazel Drummond, Elaine R. Nimmo, Dunecan Massey, Kasia Blaszczyk, Timothy Elliott, Lynn Cotterill, Helen Dallal, Alan J. Lobo, Craig Mowat, Jeremy D. Sanderson, Derek P. JewellWilliam G. Newman, Cathryn Edwards, Tariq Ahmad, John C. Mansfield, Jack Satsangi, Miles Parkes, Christopher G. Mathew, Peter Donnelly, Leena Peltonen, Jenefer M. Blackwell, Elvira Bramon, Matthew A. Brown, Juan P. Casas, Aiden Corvin, Nicholas Craddock, Panos Deloukas, Audrey Duncanson, Janusz Jankowski, Hugh S. Markus, Mark I. McCarthy, Colin N. A. Palmer, Robert Plomin, Anna Rautanen, Stephen J. Sawcer, Nilesh Samani, Richard C. Trembath, Ananth C. Viswanathan, Nicholas Wood, Chris C. A. Spencer, Celine Bellenguez, Daniel Davison, Colin Freeman, Amy Strange, Cordelia Langford, Sarah E. Hunt, Sarah Edkins, Rhian Gwilliam, Hannah Blackburn, Suzannah J. Bumpstead, Serge Dronov, Matthew Gillman, Emma Gray, Naomi Hammond, Alagurevathi Jayakumar, Owen T. McCann, Jennifer Liddle, Marc L. Perez, Simon C. Potter, Radhi Ravindrarajah, Michelle Ricketts, Matthew Waller, Paul Weston, Sara Widaa, Pamela Whittaker, Antony P. Attwood, Jonathan Stephens, Jennifer Sambrook, Willem H. Ouwehand, Wendy L. McArdle, Susan M. Ring, David P. Strachan

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Abstract

Ulcerative colitis is a common form of inflammatory bowel disease with a complex etiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome-wide association scan for ulcerative colitis in 2,361 cases and 5,417 controls. Loci showing evidence of association at P <1 x 10(-5) were followed up by genotyping in an independent set of 2,321 cases and 4,818 controls. We find genome-wide significant evidence of association at three new loci, each containing at least one biologically relevant candidate gene, on chromosomes 20q13 (HNF4A; P = 3.2 x 10(-17)), 16q22 (CDH1 and CDH3; P = 2.8 x 10(-8)) and 7q31 (LAMB1; P = 3.0 x 10(-8)). Of note, CDH1 has recently been associated with susceptibility to colorectal cancer, an established complication of longstanding ulcerative colitis. The new associations suggest that changes in the integrity of the intestinal epithelial barrier may contribute to the pathogenesis of ulcerative colitis.

Original language	English
Pages (from-to)	1330-1334
Number of pages	5
Journal	Nature Genetics
Volume	41
Issue number	12
DOIs	https://doi.org/10.1038/ng.483
Publication status	Published - Dec 2009

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Barrett, J. C., Lee, J. C., Lees, C. W., Prescott, N. J., Anderson, C. A., Phillips, A., Wesley, E., Parnell, K., Zhang, H., Drummond, H., Nimmo, E. R., Massey, D., Blaszczyk, K., Elliott, T., Cotterill, L., Dallal, H., Lobo, A. J., Mowat, C., Sanderson, J. D., ... Strachan, D. P. (2009). Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region. Nature Genetics, 41(12), 1330-1334. https://doi.org/10.1038/ng.483

@article{7fb962733b3549b9a29ffc5df495ed11,

title = "Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region",

abstract = "Ulcerative colitis is a common form of inflammatory bowel disease with a complex etiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome-wide association scan for ulcerative colitis in 2,361 cases and 5,417 controls. Loci showing evidence of association at P <1 x 10(-5) were followed up by genotyping in an independent set of 2,321 cases and 4,818 controls. We find genome-wide significant evidence of association at three new loci, each containing at least one biologically relevant candidate gene, on chromosomes 20q13 (HNF4A; P = 3.2 x 10(-17)), 16q22 (CDH1 and CDH3; P = 2.8 x 10(-8)) and 7q31 (LAMB1; P = 3.0 x 10(-8)). Of note, CDH1 has recently been associated with susceptibility to colorectal cancer, an established complication of longstanding ulcerative colitis. The new associations suggest that changes in the integrity of the intestinal epithelial barrier may contribute to the pathogenesis of ulcerative colitis.",

author = "Barrett, {Jeffrey C.} and Lee, {James C.} and Lees, {Charles W.} and Prescott, {Natalie J.} and Anderson, {Carl A.} and Anne Phillips and Emma Wesley and Kirstie Parnell and Hu Zhang and Hazel Drummond and Nimmo, {Elaine R.} and Dunecan Massey and Kasia Blaszczyk and Timothy Elliott and Lynn Cotterill and Helen Dallal and Lobo, {Alan J.} and Craig Mowat and Sanderson, {Jeremy D.} and Jewell, {Derek P.} and Newman, {William G.} and Cathryn Edwards and Tariq Ahmad and Mansfield, {John C.} and Jack Satsangi and Miles Parkes and Mathew, {Christopher G.} and Peter Donnelly and Leena Peltonen and Blackwell, {Jenefer M.} and Elvira Bramon and Brown, {Matthew A.} and Casas, {Juan P.} and Aiden Corvin and Nicholas Craddock and Panos Deloukas and Audrey Duncanson and Janusz Jankowski and Markus, {Hugh S.} and McCarthy, {Mark I.} and Palmer, {Colin N. A.} and Robert Plomin and Anna Rautanen and Sawcer, {Stephen J.} and Nilesh Samani and Trembath, {Richard C.} and Viswanathan, {Ananth C.} and Nicholas Wood and Spencer, {Chris C. A.} and Celine Bellenguez and Daniel Davison and Colin Freeman and Amy Strange and Cordelia Langford and Hunt, {Sarah E.} and Sarah Edkins and Rhian Gwilliam and Hannah Blackburn and Bumpstead, {Suzannah J.} and Serge Dronov and Matthew Gillman and Emma Gray and Naomi Hammond and Alagurevathi Jayakumar and McCann, {Owen T.} and Jennifer Liddle and Perez, {Marc L.} and Potter, {Simon C.} and Radhi Ravindrarajah and Michelle Ricketts and Matthew Waller and Paul Weston and Sara Widaa and Pamela Whittaker and Attwood, {Antony P.} and Jonathan Stephens and Jennifer Sambrook and Ouwehand, {Willem H.} and McArdle, {Wendy L.} and Ring, {Susan M.} and Strachan, {David P.}",

year = "2009",

month = dec,

doi = "10.1038/ng.483",

language = "English",

volume = "41",

pages = "1330--1334",

journal = "Nature Genetics",

issn = "1546-1718",

publisher = "Nature Research",

number = "12",

}

Barrett, JC, Lee, JC, Lees, CW, Prescott, NJ, Anderson, CA, Phillips, A, Wesley, E, Parnell, K, Zhang, H, Drummond, H, Nimmo, ER, Massey, D, Blaszczyk, K, Elliott, T, Cotterill, L, Dallal, H, Lobo, AJ, Mowat, C, Sanderson, JD, Jewell, DP, Newman, WG, Edwards, C, Ahmad, T, Mansfield, JC, Satsangi, J, Parkes, M, Mathew, CG, Donnelly, P, Peltonen, L, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Craddock, N, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, McCarthy, MI, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Samani, N, Trembath, RC, Viswanathan, AC, Wood, N, Spencer, CCA, Bellenguez, C, Davison, D, Freeman, C, Strange, A, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Perez, ML, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Attwood, AP, Stephens, J, Sambrook, J, Ouwehand, WH, McArdle, WL, Ring, SM & Strachan, DP 2009, 'Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region', Nature Genetics, vol. 41, no. 12, pp. 1330-1334. https://doi.org/10.1038/ng.483

TY - JOUR

T1 - Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region

AU - Barrett, Jeffrey C.

AU - Lee, James C.

AU - Lees, Charles W.

AU - Prescott, Natalie J.

AU - Anderson, Carl A.

AU - Phillips, Anne

AU - Wesley, Emma

AU - Parnell, Kirstie

AU - Zhang, Hu

AU - Drummond, Hazel

AU - Nimmo, Elaine R.

AU - Massey, Dunecan

AU - Blaszczyk, Kasia

AU - Elliott, Timothy

AU - Cotterill, Lynn

AU - Dallal, Helen

AU - Lobo, Alan J.

AU - Mowat, Craig

AU - Sanderson, Jeremy D.

AU - Jewell, Derek P.

AU - Newman, William G.

AU - Edwards, Cathryn

AU - Ahmad, Tariq

AU - Mansfield, John C.

AU - Satsangi, Jack

AU - Parkes, Miles

AU - Mathew, Christopher G.

AU - Donnelly, Peter

AU - Peltonen, Leena

AU - Blackwell, Jenefer M.

AU - Bramon, Elvira

AU - Brown, Matthew A.

AU - Casas, Juan P.

AU - Corvin, Aiden

AU - Craddock, Nicholas

AU - Deloukas, Panos

AU - Duncanson, Audrey

AU - Jankowski, Janusz

AU - Markus, Hugh S.

AU - McCarthy, Mark I.

AU - Palmer, Colin N. A.

AU - Plomin, Robert

AU - Rautanen, Anna

AU - Sawcer, Stephen J.

AU - Samani, Nilesh

AU - Trembath, Richard C.

AU - Viswanathan, Ananth C.

AU - Wood, Nicholas

AU - Spencer, Chris C. A.

AU - Bellenguez, Celine

AU - Davison, Daniel

AU - Freeman, Colin

AU - Strange, Amy

AU - Langford, Cordelia

AU - Hunt, Sarah E.

AU - Edkins, Sarah

AU - Gwilliam, Rhian

AU - Blackburn, Hannah

AU - Bumpstead, Suzannah J.

AU - Dronov, Serge

AU - Gillman, Matthew

AU - Gray, Emma

AU - Hammond, Naomi

AU - Jayakumar, Alagurevathi

AU - McCann, Owen T.

AU - Liddle, Jennifer

AU - Perez, Marc L.

AU - Potter, Simon C.

AU - Ravindrarajah, Radhi

AU - Ricketts, Michelle

AU - Waller, Matthew

AU - Weston, Paul

AU - Widaa, Sara

AU - Whittaker, Pamela

AU - Attwood, Antony P.

AU - Stephens, Jonathan

AU - Sambrook, Jennifer

AU - Ouwehand, Willem H.

AU - McArdle, Wendy L.

AU - Ring, Susan M.

AU - Strachan, David P.

PY - 2009/12

Y1 - 2009/12

N2 - Ulcerative colitis is a common form of inflammatory bowel disease with a complex etiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome-wide association scan for ulcerative colitis in 2,361 cases and 5,417 controls. Loci showing evidence of association at P <1 x 10(-5) were followed up by genotyping in an independent set of 2,321 cases and 4,818 controls. We find genome-wide significant evidence of association at three new loci, each containing at least one biologically relevant candidate gene, on chromosomes 20q13 (HNF4A; P = 3.2 x 10(-17)), 16q22 (CDH1 and CDH3; P = 2.8 x 10(-8)) and 7q31 (LAMB1; P = 3.0 x 10(-8)). Of note, CDH1 has recently been associated with susceptibility to colorectal cancer, an established complication of longstanding ulcerative colitis. The new associations suggest that changes in the integrity of the intestinal epithelial barrier may contribute to the pathogenesis of ulcerative colitis.

AB - Ulcerative colitis is a common form of inflammatory bowel disease with a complex etiology. As part of the Wellcome Trust Case Control Consortium 2, we performed a genome-wide association scan for ulcerative colitis in 2,361 cases and 5,417 controls. Loci showing evidence of association at P <1 x 10(-5) were followed up by genotyping in an independent set of 2,321 cases and 4,818 controls. We find genome-wide significant evidence of association at three new loci, each containing at least one biologically relevant candidate gene, on chromosomes 20q13 (HNF4A; P = 3.2 x 10(-17)), 16q22 (CDH1 and CDH3; P = 2.8 x 10(-8)) and 7q31 (LAMB1; P = 3.0 x 10(-8)). Of note, CDH1 has recently been associated with susceptibility to colorectal cancer, an established complication of longstanding ulcerative colitis. The new associations suggest that changes in the integrity of the intestinal epithelial barrier may contribute to the pathogenesis of ulcerative colitis.

U2 - 10.1038/ng.483

DO - 10.1038/ng.483

M3 - Article

SN - 1546-1718

VL - 41

SP - 1330

EP - 1334

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region

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