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

Research output: Contribution to journalArticle

429 Scopus citations

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 × 10-10), 16q22.1 (rs9929218, CDH1; P = 1.2 × 10-8), 19q13.1 (rs10411210, RHPN2; P = 4.6 × 10-9) and 20p12.3 (rs961253; P = 2.0 × 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 languageEnglish (US)
Pages (from-to)1426-1435
Number of pages10
JournalNature Genetics
Volume40
Issue number12
DOIs
StatePublished - Dec 2008
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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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., ... Dunlop, M. G. (2008). Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer. Nature Genetics, 40(12), 1426-1435. https://doi.org/10.1038/ng.262