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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.

SUBMITTER: COGENT Study 

PROVIDER: S-EPMC2836775 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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

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

Nature genetics 20081116 12


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 unreporte  ...[more]

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