期刊
NATURE GENETICS
卷 40, 期 5, 页码 623-630出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.111
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资金
- Cancer Research UK [C348/A3758, A8896, C48/A6361] Funding Source: Medline
- Medical Research Council [MC_U127527198, G0000657-53203, G0301096] Funding Source: Medline
- Chief Scientist Office [CZB/4/449] Funding Source: Medline
- MRC [MC_U127527198, G0301096] Funding Source: UKRI
- Chief Scientist Office [CZB/4/449] Funding Source: researchfish
- Medical Research Council [G0301096, MC_U127527198] Funding Source: researchfish
To identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls. In phase 3, we evaluated 11 SNPs showing association at P < 10(-4) in a joint analysis of phases 1 and 2 in 4,287 CRC cases and 3,743 controls. Two SNPs were taken forward to phase 4 genotyping ( 10,731 CRC cases and 10,961 controls from eight centers). In addition to the previously reported 8q24, 15q13 and 18q21 CRC risk loci, we identified two previously unreported associations: rs10795668, located at 10p14 (P=2.5 x 10(-13) overall; P=6.9 x 10(-12) replication), and rs16892766, at 8q23.3 (P=3.3 x 10(-18) overall; P=9.6 x 10(-17) replication), which tags a plausible causative gene, EIF3H. These data provide further evidence for the 'common-disease common-variant' model of CRC predisposition.
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