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Meta-Analysis

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

COGENT Study et al. Nat Genet. 2008 Dec.

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.

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Figures

Figure 1
Figure 1
Regional plots of the four confirmed associations (14q22.2, 16q22.1, 19q13.1 and 20p12.3). Each panel shows single-marker association statistics (as −log10 P) from the combined analysis of phase 1 (red), phases 1 and 2 (blue) and all phases (yellow) as a function of genomic position (NCBI build 36.1). Recombination rate across each region in HapMap CEU shown in black (right y axis). Also shown are the relative position of genes mapping to each region of association.
Figure 2
Figure 2
Forest plot of effect size and direction for the four SNPs associated with CRC. (a) rs961253. (b) rs4444235. (c) rs10411210. (d) rs9929218. Boxes denote allelic OR point estimates, their areas being proportional to the inverse variance weight of the estimate. Horizontal lines represent 95% CIs. The diamond (and broken line) represents the summary OR computed under a fixed-effects model, with the 95% CI given by its width. The unbroken vertical line is at the null value (OR = 1.0).
Figure 3
Figure 3
Power of the meta-analysis to identify each of the ten colorectal cancer susceptibility alleles, stipulating a P value of 10−5. Genotypic risks associated with each locus derived from replication data.
See this image and copyright information in PMC

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