Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Su, Zhan, Gay, Laura J., Strange, Amy, Palles, Claire, Band, Gavin, Whiteman, David C., Lescai, Francesco, Langford, Cordelia, Nanji, Manoj, Edkins, Sarah, van der Winkel, Anouk, Levine, David, Sasieni, Peter, Bellenguez, Celine, Howarth, Kimberley, Freeman, Colin, Trudgill, Nigel, Tucker, Art T., Pirinen, Matti, Peppelenbosch, Maikel P., van der Laan, Luc J. W., Kuipers, Ernst J., Drenth, Joost P. H., Peters, Wilbert H., Reynolds, John V., Kelleher, Dermot P., McManus, Ross, Grabsch, Heike, Prenen, Hans, Bisschops, Raf, Krishnadath, Kausila, Siersema, Peter D., van Baal, Jantine W. P. M., Middleton, Mark, Petty, Russell, Gillies, Richard, Burch, Nicola, Bhandari, Pradeep, Paterson, Stuart, Edwards, Cathryn, Penman, Ian, Vaidya, Kishor, Ang, Yeng, Murray, Iain, Patel, Praful, Ye, Weimin, Mullins, Paul, Wu, Anna H., Bird, Nigel C., Dallal, Helen, Shaheen, Nicholas J., Murray, Liam J., Koss, Konrad, Bernstein, Leslie, Romero, Yvonne, Hardie, Laura J., Zhang, Rui, Winter, Helen, Corley, Douglas A., Panter, Simon, Risch, Harvey A., Reid, Brian J., Sargeant, Ian, Gammon, Marilie D., Smart, Howard, Dhar, Anjan, McMurtry, Hugh, Ali, Haythem, Liu, Geoffrey, Casson, Alan G., Chow, Wong-Ho, Rutter, Matt, Tawil, Ashref, Morris, Danielle, Nwokolo, Chuka, Isaacs, Peter, Rodgers, Colin, Ragunath, Krish, MacDonald, Chris, Haigh, Chris, Monk, David, Davies, Gareth, Wajed, Saj, Johnston, David, Gibbons, Michael, Cullen, Sue, Church, Nicholas, Langley, Ruth, Griffin, Michael, Alderson, Derek, Deloukas, Panos, Hunt, Sarah E., Gray, Emma, Dronov, Serge, Potter, Simon C., Tashakkori-Ghanbaria, Avazeh, Anderson, Mark, Brooks, Claire, Blackwell, Jenefer M., Bramon, Elvira, Brown, Matthew A., Casas, Juan P., Corvin, Aiden, Duncanson, Audrey, Markus, Hugh S., Mathew, Christopher G., Palmer, Colin N. A., Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J., Trembath, Richard C., Viswanathan, Ananth C., Wood, Nicholas, Trynka, Gosia, Wijmenga, Cisca, Cazier, Jean-Baptiste, Atherfold, Paul, Nicholson, Anna M., Gellatly, Nichola L., Glancy, Deborah, Cooper, Sheldon C., Cunningham, David, Lind, Tore, Hapeshi, Julie, Ferry, David, Rathbone, Barrie, Brown, Julia, Love, Sharon, Attwood, Stephen, MacGregor, Stuart, Watson, Peter, Sanders, Scott, Ek, Weronica, Harrison, Rebecca F., Moayyedi, Paul, de Caestecker, John, Barr, Hugh, Stupka, Elia, Vaughan, Thomas L., Peltonen, Leena, Spencer, Chris C. A., Tomlinson, Ian, Donnelly, Peter and Jankowski, Janusz A. Z. (2012) Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus. Nature Genetics, 44 10: 1131-1136. doi:10.1038/ng.2408


Author Su, Zhan
Gay, Laura J.
Strange, Amy
Palles, Claire
Band, Gavin
Whiteman, David C.
Lescai, Francesco
Langford, Cordelia
Nanji, Manoj
Edkins, Sarah
van der Winkel, Anouk
Levine, David
Sasieni, Peter
Bellenguez, Celine
Howarth, Kimberley
Freeman, Colin
Trudgill, Nigel
Tucker, Art T.
Pirinen, Matti
Peppelenbosch, Maikel P.
van der Laan, Luc J. W.
Kuipers, Ernst J.
Drenth, Joost P. H.
Peters, Wilbert H.
Reynolds, John V.
Kelleher, Dermot P.
McManus, Ross
Grabsch, Heike
Prenen, Hans
Bisschops, Raf
Krishnadath, Kausila
Siersema, Peter D.
van Baal, Jantine W. P. M.
Middleton, Mark
Petty, Russell
Gillies, Richard
Burch, Nicola
Bhandari, Pradeep
Paterson, Stuart
Edwards, Cathryn
Penman, Ian
Vaidya, Kishor
Ang, Yeng
Murray, Iain
Patel, Praful
Ye, Weimin
Mullins, Paul
Wu, Anna H.
Bird, Nigel C.
Dallal, Helen
Shaheen, Nicholas J.
Murray, Liam J.
Koss, Konrad
Bernstein, Leslie
Romero, Yvonne
Hardie, Laura J.
Zhang, Rui
Winter, Helen
Corley, Douglas A.
Panter, Simon
Risch, Harvey A.
Reid, Brian J.
Sargeant, Ian
Gammon, Marilie D.
Smart, Howard
Dhar, Anjan
McMurtry, Hugh
Ali, Haythem
Liu, Geoffrey
Casson, Alan G.
Chow, Wong-Ho
Rutter, Matt
Tawil, Ashref
Morris, Danielle
Nwokolo, Chuka
Isaacs, Peter
Rodgers, Colin
Ragunath, Krish
MacDonald, Chris
Haigh, Chris
Monk, David
Davies, Gareth
Wajed, Saj
Johnston, David
Gibbons, Michael
Cullen, Sue
Church, Nicholas
Langley, Ruth
Griffin, Michael
Alderson, Derek
Deloukas, Panos
Hunt, Sarah E.
Gray, Emma
Dronov, Serge
Potter, Simon C.
Tashakkori-Ghanbaria, Avazeh
Anderson, Mark
Brooks, Claire
Blackwell, Jenefer M.
Bramon, Elvira
Brown, Matthew A.
Casas, Juan P.
Corvin, Aiden
Duncanson, Audrey
Markus, Hugh S.
Mathew, Christopher G.
Palmer, Colin N. A.
Plomin, Robert
Rautanen, Anna
Sawcer, Stephen J.
Trembath, Richard C.
Viswanathan, Ananth C.
Wood, Nicholas
Trynka, Gosia
Wijmenga, Cisca
Cazier, Jean-Baptiste
Atherfold, Paul
Nicholson, Anna M.
Gellatly, Nichola L.
Glancy, Deborah
Cooper, Sheldon C.
Cunningham, David
Lind, Tore
Hapeshi, Julie
Ferry, David
Rathbone, Barrie
Brown, Julia
Love, Sharon
Attwood, Stephen
MacGregor, Stuart
Watson, Peter
Sanders, Scott
Ek, Weronica
Harrison, Rebecca F.
Moayyedi, Paul
de Caestecker, John
Barr, Hugh
Stupka, Elia
Vaughan, Thomas L.
Peltonen, Leena
Spencer, Chris C. A.
Tomlinson, Ian
Donnelly, Peter
Jankowski, Janusz A. Z.
Total Author Count Override 144
Title Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
1546-1718
Publication date 2012-10
Sub-type Article (original research)
DOI 10.1038/ng.2408
Volume 44
Issue 10
Start page 1131
End page 1136
Total pages 6
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Collection year 2013
Language eng
Formatted abstract
Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P combined = 4.09 × 10 -9; odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P combined = 2.74 × 10 -10; OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
Keyword Genome-wide association
Gastroesophageal-reflux disease
Susceptibility loci
Risk-factors
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online 9 September 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
UQ Diamantina Institute Publications
 
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