Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer

Richard S Houlston; Emily Webb; Peter Broderick; Alan M Pittman; Maria Chiara Di Bernardo; Steven Lubbe; Ian Chandler; Jayaram Vijayakrishnan; Kate Sullivan; Steven Penegar; Luis Carvajal-Carmona; Kimberley Howarth; Emma Jaeger; Sarah L Spain; Axel Walther; Ella Barclay; Lynn Martin; Maggie Gorman; Enric Domingo; Ana S Teixeira; David Kerr; Jean-Baptiste Cazier; Iina Niittymäki; Sari Tuupanen; Auli Karhu; Lauri A Aaltonen; Ian P M Tomlinson; Susan M Farrington; Albert Tenesa; James G D Prendergast; Rebecca A Barnetson; Roseanne Cetnarskyj; Mary E Porteous; Paul D P Pharoah; Thibaud Koessler; Jochen Hampe; Stephan Buch; Clemens Schafmayer; Jurgen Tepel; Stefan Schreiber; Henry Völzke; Jenny Chang-Claude; Michael Hoffmeister; Hermann Brenner; Brent W Zanke; Alexandre Montpetit; Thomas J Hudson; Steven Gallinger; Harry Campbell; Malcolm G Dunlop; COGENT Consortium

doi:10.1038/ng.262

Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer

Richard S Houlston, Emily Webb, Peter Broderick, Alan M Pittman, Maria Chiara Di Bernardo, Steven Lubbe, Ian Chandler, Jayaram Vijayakrishnan, Kate Sullivan, Steven Penegar, Luis Carvajal-Carmona, Kimberley Howarth, Emma Jaeger, Sarah L Spain, Axel Walther, Ella Barclay, Lynn Martin, Maggie Gorman, Enric Domingo, Ana S TeixeiraDavid Kerr, Jean-Baptiste Cazier, Iina Niittymäki, Sari Tuupanen, Auli Karhu, Lauri A Aaltonen, Ian P M Tomlinson, Susan M Farrington, Albert Tenesa, James G D Prendergast, Rebecca A Barnetson, Roseanne Cetnarskyj, Mary E Porteous, Paul D P Pharoah, Thibaud Koessler, Jochen Hampe, Stephan Buch, Clemens Schafmayer, Jurgen Tepel, Stefan Schreiber, Henry Völzke, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner, Brent W Zanke, Alexandre Montpetit, Thomas J Hudson, Steven Gallinger, Harry Campbell, Malcolm G Dunlop, COGENT Consortium

Cancer and Genomic Sciences

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

443 Citations (Scopus)

Abstract

Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly influence the risk of developing colorectal cancer (CRC). To enhance power to identify additional loci with similar effect sizes, we conducted a meta-analysis of two GWA studies, comprising 13,315 individuals genotyped for 38,710 common tagging SNPs. We undertook replication testing in up to eight independent case-control series comprising 27,418 subjects. We identified four previously unreported CRC risk loci at 14q22.2 (rs4444235, BMP4; P = 8.1 x 10(-10)), 16q22.1 (rs9929218, CDH1; P = 1.2 x 10(-8)), 19q13.1 (rs10411210, RHPN2; P = 4.6 x 10(-9)) and 20p12.3 (rs961253; P = 2.0 x 10(-10)). These findings underscore the value of large sample series for discovery and follow-up of genetic variants contributing to the etiology of CRC.

Original language	English
Pages (from-to)	1426-35
Number of pages	10
Journal	Nature Genetics
Volume	40
Issue number	12
DOIs	https://doi.org/10.1038/ng.262
Publication status	Published - Dec 2008

Keywords

Aged
Case-Control Studies
Colorectal Neoplasms
Female
Genetic Predisposition to Disease
Genome, Human
Genome-Wide Association Study
Humans
Male
Middle Aged

UN SDGs

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

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10.1038/ng.262

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Houlston, R. S., Webb, E., Broderick, P., Pittman, A. M., Di Bernardo, M. C., Lubbe, S., Chandler, I., Vijayakrishnan, J., Sullivan, K., Penegar, S., Carvajal-Carmona, L., Howarth, K., Jaeger, E., Spain, S. L., Walther, A., Barclay, E., Martin, L., Gorman, M., Domingo, E., ... COGENT Consortium (2008). Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer. Nature Genetics, 40(12), 1426-35. https://doi.org/10.1038/ng.262

@article{af7781c89914403a8b15fc751b124aca,

title = "Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer",

abstract = "Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly influence the risk of developing colorectal cancer (CRC). To enhance power to identify additional loci with similar effect sizes, we conducted a meta-analysis of two GWA studies, comprising 13,315 individuals genotyped for 38,710 common tagging SNPs. We undertook replication testing in up to eight independent case-control series comprising 27,418 subjects. We identified four previously unreported CRC risk loci at 14q22.2 (rs4444235, BMP4; P = 8.1 x 10(-10)), 16q22.1 (rs9929218, CDH1; P = 1.2 x 10(-8)), 19q13.1 (rs10411210, RHPN2; P = 4.6 x 10(-9)) and 20p12.3 (rs961253; P = 2.0 x 10(-10)). These findings underscore the value of large sample series for discovery and follow-up of genetic variants contributing to the etiology of CRC.",

keywords = "Aged, Case-Control Studies, Colorectal Neoplasms, Female, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Male, Middle Aged",

author = "Houlston, {Richard S} and Emily Webb and Peter Broderick and Pittman, {Alan M} and {Di Bernardo}, {Maria Chiara} and Steven Lubbe and Ian Chandler and Jayaram Vijayakrishnan and Kate Sullivan and Steven Penegar and Luis Carvajal-Carmona and Kimberley Howarth and Emma Jaeger and Spain, {Sarah L} and Axel Walther and Ella Barclay and Lynn Martin and Maggie Gorman and Enric Domingo and Teixeira, {Ana S} and David Kerr and Jean-Baptiste Cazier and Iina Niittym{\"a}ki and Sari Tuupanen and Auli Karhu and Aaltonen, {Lauri A} and Tomlinson, {Ian P M} and Farrington, {Susan M} and Albert Tenesa and Prendergast, {James G D} and Barnetson, {Rebecca A} and Roseanne Cetnarskyj and Porteous, {Mary E} and Pharoah, {Paul D P} and Thibaud Koessler and Jochen Hampe and Stephan Buch and Clemens Schafmayer and Jurgen Tepel and Stefan Schreiber and Henry V{\"o}lzke and Jenny Chang-Claude and Michael Hoffmeister and Hermann Brenner and Zanke, {Brent W} and Alexandre Montpetit and Hudson, {Thomas J} and Steven Gallinger and Harry Campbell and Dunlop, {Malcolm G} and {COGENT Consortium}",

year = "2008",

month = dec,

doi = "10.1038/ng.262",

language = "English",

volume = "40",

pages = "1426--35",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "12",

}

Houlston, RS, Webb, E, Broderick, P, Pittman, AM, Di Bernardo, MC, Lubbe, S, Chandler, I, Vijayakrishnan, J, Sullivan, K, Penegar, S, Carvajal-Carmona, L, Howarth, K, Jaeger, E, Spain, SL, Walther, A, Barclay, E, Martin, L, Gorman, M, Domingo, E, Teixeira, AS, Kerr, D, Cazier, J-B, Niittymäki, I, Tuupanen, S, Karhu, A, Aaltonen, LA, Tomlinson, IPM, Farrington, SM, Tenesa, A, Prendergast, JGD, Barnetson, RA, Cetnarskyj, R, Porteous, ME, Pharoah, PDP, Koessler, T, Hampe, J, Buch, S, Schafmayer, C, Tepel, J, Schreiber, S, Völzke, H, Chang-Claude, J, Hoffmeister, M, Brenner, H, Zanke, BW, Montpetit, A, Hudson, TJ, Gallinger, S, Campbell, H, Dunlop, MG & COGENT Consortium 2008, 'Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer', Nature Genetics, vol. 40, no. 12, pp. 1426-35. https://doi.org/10.1038/ng.262

TY - JOUR

T1 - Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer

AU - Houlston, Richard S

AU - Webb, Emily

AU - Broderick, Peter

AU - Pittman, Alan M

AU - Di Bernardo, Maria Chiara

AU - Lubbe, Steven

AU - Chandler, Ian

AU - Vijayakrishnan, Jayaram

AU - Sullivan, Kate

AU - Penegar, Steven

AU - Carvajal-Carmona, Luis

AU - Howarth, Kimberley

AU - Jaeger, Emma

AU - Spain, Sarah L

AU - Walther, Axel

AU - Barclay, Ella

AU - Martin, Lynn

AU - Gorman, Maggie

AU - Domingo, Enric

AU - Teixeira, Ana S

AU - Kerr, David

AU - Cazier, Jean-Baptiste

AU - Niittymäki, Iina

AU - Tuupanen, Sari

AU - Karhu, Auli

AU - Aaltonen, Lauri A

AU - Tomlinson, Ian P M

AU - Farrington, Susan M

AU - Tenesa, Albert

AU - Prendergast, James G D

AU - Barnetson, Rebecca A

AU - Cetnarskyj, Roseanne

AU - Porteous, Mary E

AU - Pharoah, Paul D P

AU - Koessler, Thibaud

AU - Hampe, Jochen

AU - Buch, Stephan

AU - Schafmayer, Clemens

AU - Tepel, Jurgen

AU - Schreiber, Stefan

AU - Völzke, Henry

AU - Chang-Claude, Jenny

AU - Hoffmeister, Michael

AU - Brenner, Hermann

AU - Zanke, Brent W

AU - Montpetit, Alexandre

AU - Hudson, Thomas J

AU - Gallinger, Steven

AU - Campbell, Harry

AU - Dunlop, Malcolm G

AU - COGENT Consortium

PY - 2008/12

Y1 - 2008/12

N2 - Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly influence the risk of developing colorectal cancer (CRC). To enhance power to identify additional loci with similar effect sizes, we conducted a meta-analysis of two GWA studies, comprising 13,315 individuals genotyped for 38,710 common tagging SNPs. We undertook replication testing in up to eight independent case-control series comprising 27,418 subjects. We identified four previously unreported CRC risk loci at 14q22.2 (rs4444235, BMP4; P = 8.1 x 10(-10)), 16q22.1 (rs9929218, CDH1; P = 1.2 x 10(-8)), 19q13.1 (rs10411210, RHPN2; P = 4.6 x 10(-9)) and 20p12.3 (rs961253; P = 2.0 x 10(-10)). These findings underscore the value of large sample series for discovery and follow-up of genetic variants contributing to the etiology of CRC.

AB - Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly influence the risk of developing colorectal cancer (CRC). To enhance power to identify additional loci with similar effect sizes, we conducted a meta-analysis of two GWA studies, comprising 13,315 individuals genotyped for 38,710 common tagging SNPs. We undertook replication testing in up to eight independent case-control series comprising 27,418 subjects. We identified four previously unreported CRC risk loci at 14q22.2 (rs4444235, BMP4; P = 8.1 x 10(-10)), 16q22.1 (rs9929218, CDH1; P = 1.2 x 10(-8)), 19q13.1 (rs10411210, RHPN2; P = 4.6 x 10(-9)) and 20p12.3 (rs961253; P = 2.0 x 10(-10)). These findings underscore the value of large sample series for discovery and follow-up of genetic variants contributing to the etiology of CRC.

KW - Aged

KW - Case-Control Studies

KW - Colorectal Neoplasms

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Middle Aged

U2 - 10.1038/ng.262

DO - 10.1038/ng.262

M3 - Article

C2 - 19011631

SN - 1061-4036

VL - 40

SP - 1426

EP - 1435

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer

Abstract

Keywords

UN SDGs

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