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

Zhan Su; Laura J Gay; Amy Strange; Claire Palles; Gavin Band; David C Whiteman; Francesco Lescai; Cordelia Langford; Manoj Nanji; Sarah Edkins; Anouk van der Winkel; David Levine; Peter Sasieni; Céline Bellenguez; Kimberley Howarth; Colin Freeman; Nigel Trudgill; Art T Tucker; Matti Pirinen; Maikel P Peppelenbosch; Luc J W van der Laan; Ernst J Kuipers; Joost P H Drenth; Wilbert H Peters; John V Reynolds; Dermot P Kelleher; Ross McManus; Heike Grabsch; Hans Prenen; Raf Bisschops; Kausila Krishnadath; Peter D Siersema; Jantine W P M van Baal; Mark Middleton; Russell Petty; Richard Gillies; Nicola Burch; Pradeep Bhandari; Stuart Paterson; Cathryn Edwards; Derek Alderson; Emma Gray; Mark Anderson; Jean-Baptiste Cazier; Sheldon C Cooper; David Ferry; Peter Watson; Rebecca F Harrison; Paul Moayyedi; Janusz A Z Jankowski; Esophageal Adenocarcinoma Genetics Consortium

doi:10.1038/ng.2408

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

Zhan Su, Laura J Gay, Amy Strange, Claire Palles, Gavin Band, David C Whiteman, Francesco Lescai, Cordelia Langford, Manoj Nanji, Sarah Edkins, Anouk van der Winkel, David Levine, Peter Sasieni, Céline Bellenguez, Kimberley Howarth, Colin Freeman, Nigel Trudgill, Art T Tucker, Matti Pirinen, Maikel P PeppelenboschLuc J W van der Laan, Ernst J Kuipers, Joost P H Drenth, Wilbert H Peters, John V Reynolds, Dermot P Kelleher, Ross McManus, Heike Grabsch, Hans Prenen, Raf Bisschops, Kausila Krishnadath, Peter D Siersema, Jantine W P M van Baal, Mark Middleton, Russell Petty, Richard Gillies, Nicola Burch, Pradeep Bhandari, Stuart Paterson, Cathryn Edwards, Derek Alderson, Emma Gray, Mark Anderson, Jean-Baptiste Cazier, Sheldon C Cooper, David Ferry, Peter Watson, Rebecca F Harrison, Paul Moayyedi, Janusz A Z Jankowski, Esophageal Adenocarcinoma Genetics Consortium

Research output: Contribution to journal › Article › peer-review

125 Citations (Scopus)

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 (Pcombined=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 (Pcombined=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.

Original language	English
Pages (from-to)	1131-6
Number of pages	6
Journal	Nature Genetics
Volume	44
Issue number	10
DOIs	https://doi.org/10.1038/ng.2408
Publication status	Published - Oct 2012

Keywords

Adult
Aged
Barrett Esophagus
Case-Control Studies
Chromosomes, Human, Pair 16
Female
Gene Frequency
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Linkage Disequilibrium
Major Histocompatibility Complex
Male
Middle Aged
Models, Genetic
Polymorphism, Single Nucleotide

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ng.2408

Cite this

Su, Z., Gay, L. J., Strange, A., Palles, C., Band, G., Whiteman, D. C., Lescai, F., Langford, C., Nanji, M., Edkins, S., van der Winkel, A., Levine, D., Sasieni, P., Bellenguez, C., Howarth, K., Freeman, C., Trudgill, N., Tucker, A. T., Pirinen, M., ... Esophageal Adenocarcinoma Genetics Consortium (2012). Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus. Nature Genetics, 44(10), 1131-6. https://doi.org/10.1038/ng.2408

@article{b3fe2e15e4124be180a7b048ce0601f7,

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

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 (Pcombined=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 (Pcombined=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.",

keywords = "Adult, Aged, Barrett Esophagus, Case-Control Studies, Chromosomes, Human, Pair 16, Female, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Major Histocompatibility Complex, Male, Middle Aged, Models, Genetic, Polymorphism, Single Nucleotide",

author = "Zhan Su and Gay, {Laura J} and Amy Strange and Claire Palles and Gavin Band and Whiteman, {David C} and Francesco Lescai and Cordelia Langford and Manoj Nanji and Sarah Edkins and {van der Winkel}, Anouk and David Levine and Peter Sasieni and C{\'e}line Bellenguez and Kimberley Howarth and Colin Freeman and Nigel Trudgill and Tucker, {Art T} and Matti Pirinen and Peppelenbosch, {Maikel P} and {van der Laan}, {Luc J W} and Kuipers, {Ernst J} and Drenth, {Joost P H} and Peters, {Wilbert H} and Reynolds, {John V} and Kelleher, {Dermot P} and Ross McManus and Heike Grabsch and Hans Prenen and Raf Bisschops and Kausila Krishnadath and Siersema, {Peter D} and {van Baal}, {Jantine W P M} and Mark Middleton and Russell Petty and Richard Gillies and Nicola Burch and Pradeep Bhandari and Stuart Paterson and Cathryn Edwards and Derek Alderson and Emma Gray and Mark Anderson and Jean-Baptiste Cazier and Cooper, {Sheldon C} and David Ferry and Peter Watson and Harrison, {Rebecca F} and Paul Moayyedi and Jankowski, {Janusz A Z} and {Esophageal Adenocarcinoma Genetics Consortium}",

year = "2012",

month = oct,

doi = "10.1038/ng.2408",

language = "English",

volume = "44",

pages = "1131--6",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "10",

}

Su, Z, Gay, LJ, Strange, A, Palles, C, Band, G, Whiteman, DC, Lescai, F, Langford, C, Nanji, M, Edkins, S, van der Winkel, A, Levine, D, Sasieni, P, Bellenguez, C, Howarth, K, Freeman, C, Trudgill, N, Tucker, AT, Pirinen, M, Peppelenbosch, MP, van der Laan, LJW, Kuipers, EJ, Drenth, JPH, Peters, WH, Reynolds, JV, Kelleher, DP, McManus, R, Grabsch, H, Prenen, H, Bisschops, R, Krishnadath, K, Siersema, PD, van Baal, JWPM, Middleton, M, Petty, R, Gillies, R, Burch, N, Bhandari, P, Paterson, S, Edwards, C, Alderson, D, Gray, E, Anderson, M, Cazier, J-B, Cooper, SC, Ferry, D, Watson, P, Harrison, RF, Moayyedi, P, Jankowski, JAZ & Esophageal Adenocarcinoma Genetics Consortium 2012, 'Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus', Nature Genetics, vol. 44, no. 10, pp. 1131-6. https://doi.org/10.1038/ng.2408

TY - JOUR

T1 - Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

AU - Su, Zhan

AU - Gay, Laura J

AU - Strange, Amy

AU - Palles, Claire

AU - Band, Gavin

AU - Whiteman, David C

AU - Lescai, Francesco

AU - Langford, Cordelia

AU - Nanji, Manoj

AU - Edkins, Sarah

AU - van der Winkel, Anouk

AU - Levine, David

AU - Sasieni, Peter

AU - Bellenguez, Céline

AU - Howarth, Kimberley

AU - Freeman, Colin

AU - Trudgill, Nigel

AU - Tucker, Art T

AU - Pirinen, Matti

AU - Peppelenbosch, Maikel P

AU - van der Laan, Luc J W

AU - Kuipers, Ernst J

AU - Drenth, Joost P H

AU - Peters, Wilbert H

AU - Reynolds, John V

AU - Kelleher, Dermot P

AU - McManus, Ross

AU - Grabsch, Heike

AU - Prenen, Hans

AU - Bisschops, Raf

AU - Krishnadath, Kausila

AU - Siersema, Peter D

AU - van Baal, Jantine W P M

AU - Middleton, Mark

AU - Petty, Russell

AU - Gillies, Richard

AU - Burch, Nicola

AU - Bhandari, Pradeep

AU - Paterson, Stuart

AU - Edwards, Cathryn

AU - Alderson, Derek

AU - Gray, Emma

AU - Anderson, Mark

AU - Cazier, Jean-Baptiste

AU - Cooper, Sheldon C

AU - Ferry, David

AU - Watson, Peter

AU - Harrison, Rebecca F

AU - Moayyedi, Paul

AU - Jankowski, Janusz A Z

AU - Esophageal Adenocarcinoma Genetics Consortium

PY - 2012/10

Y1 - 2012/10

N2 - 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 (Pcombined=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 (Pcombined=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.

AB - 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 (Pcombined=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 (Pcombined=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.

KW - Adult

KW - Aged

KW - Barrett Esophagus

KW - Case-Control Studies

KW - Chromosomes, Human, Pair 16

KW - Female

KW - Gene Frequency

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Linkage Disequilibrium

KW - Major Histocompatibility Complex

KW - Male

KW - Middle Aged

KW - Models, Genetic

KW - Polymorphism, Single Nucleotide

U2 - 10.1038/ng.2408

DO - 10.1038/ng.2408

M3 - Article

C2 - 22961001

SN - 1061-4036

VL - 44

SP - 1131

EP - 1136

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this