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Meta-Analysis
. 2012 May 27;44(7):770-6.
doi: 10.1038/ng.2293.

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

Malcolm G Dunlop  1 , Sara E Dobbins, Susan Mary Farrington, Angela M Jones, Claire Palles, Nicola Whiffin, Albert Tenesa, Sarah Spain, Peter Broderick, Li-Yin Ooi, Enric Domingo, Claire Smillie, Marc Henrion, Matthew Frampton, Lynn Martin, Graeme Grimes, Maggie Gorman, Colin Semple, Yusanne P Ma, Ella Barclay, James Prendergast, Jean-Baptiste Cazier, Bianca Olver, Steven Penegar, Steven Lubbe, Ian Chander, Luis G Carvajal-Carmona, Stephane Ballereau, Amy Lloyd, Jayaram Vijayakrishnan, Lina Zgaga, Igor Rudan, Evropi Theodoratou; Colorectal Tumour Gene Identification (CORGI) Consortium; John M Starr, Ian Deary, Iva Kirac, Dujo Kovacević, Lauri A Aaltonen, Laura Renkonen-Sinisalo, Jukka-Pekka Mecklin, Koichi Matsuda, Yusuke Nakamura, Yukinori Okada, Steven Gallinger, David J Duggan, David Conti, Polly Newcomb, John Hopper, Mark A Jenkins, Fredrick Schumacher, Graham Casey, Douglas Easton, Mitul Shah, Paul Pharoah, Annika Lindblom, Tao Liu; Swedish Low-Risk Colorectal Cancer Study Group; Christopher G Smith, Hannah West, Jeremy P Cheadle; COIN Collaborative Group; Rachel Midgley, David J Kerr, Harry Campbell, Ian P Tomlinson, Richard S Houlston
Collaborators, Affiliations
Meta-Analysis

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

Malcolm G Dunlop et al. Nat Genet. .

Abstract

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.

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Figures

Figure 1
Figure 1. Regional plots of association results and recombination rates for the 6p21, 11q13.4, Xp22.2 susceptibility loci
(a-d) Association results of both genotyped (triangles) and imputed (circles) SNPs in the GWAS samples and recombination rates within the loci: (a) 6p21, (b), 11q13.4, (c) Xp22.2. For each plot, −log10 P values (y axis) of the SNPs are shown according to their chromosomal positions (x axis). The top genotyped SNP in each combined analysis is a large triangle and is labelled by its rsID. The colour intensity of each symbol reflects the extent of LD with the top genotyped SNP: white (r2=0) through to dark red (r2=1.0). Genetic recombination rates (cM/Mb), estimated using HapMap CEU samples, are shown with a light blue line. Physical positions are based on NCBI build 36 of the human genome. Also shown are the relative positions of genes and transcripts mapping to each region of association. Genes have been redrawn to show the relative positions; therefore, maps are not to physical scale.
Figure 1
Figure 1. Regional plots of association results and recombination rates for the 6p21, 11q13.4, Xp22.2 susceptibility loci
(a-d) Association results of both genotyped (triangles) and imputed (circles) SNPs in the GWAS samples and recombination rates within the loci: (a) 6p21, (b), 11q13.4, (c) Xp22.2. For each plot, −log10 P values (y axis) of the SNPs are shown according to their chromosomal positions (x axis). The top genotyped SNP in each combined analysis is a large triangle and is labelled by its rsID. The colour intensity of each symbol reflects the extent of LD with the top genotyped SNP: white (r2=0) through to dark red (r2=1.0). Genetic recombination rates (cM/Mb), estimated using HapMap CEU samples, are shown with a light blue line. Physical positions are based on NCBI build 36 of the human genome. Also shown are the relative positions of genes and transcripts mapping to each region of association. Genes have been redrawn to show the relative positions; therefore, maps are not to physical scale.
Figure 1
Figure 1. Regional plots of association results and recombination rates for the 6p21, 11q13.4, Xp22.2 susceptibility loci
(a-d) Association results of both genotyped (triangles) and imputed (circles) SNPs in the GWAS samples and recombination rates within the loci: (a) 6p21, (b), 11q13.4, (c) Xp22.2. For each plot, −log10 P values (y axis) of the SNPs are shown according to their chromosomal positions (x axis). The top genotyped SNP in each combined analysis is a large triangle and is labelled by its rsID. The colour intensity of each symbol reflects the extent of LD with the top genotyped SNP: white (r2=0) through to dark red (r2=1.0). Genetic recombination rates (cM/Mb), estimated using HapMap CEU samples, are shown with a light blue line. Physical positions are based on NCBI build 36 of the human genome. Also shown are the relative positions of genes and transcripts mapping to each region of association. Genes have been redrawn to show the relative positions; therefore, maps are not to physical scale.
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