Journal
SCIENTIFIC REPORTS
Volume 5, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/srep10442
Keywords
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Funding
- Cancer Research UK
- Medical Research Council
- National Institute of Health Research Cancer Research Network
- Bobby Moore Fund from Cancer Research UK
- Tenovus
- Kidani Trust
- Cancer Research Wales
- National Institute for Social Care and Health Research Cancer Genetics Biomedical Research Unit
- KFSHRC
- Cancer Research UK (Bobby Moore Fund for Cancer Research UK) [C1298/A8362]
- National Cancer Research Network
- NHS via the Biological Research Centre of the National Institute for Health Research at the Royal Marsden Hospital NHS Trust
- ICR
- Sir John Fisher Foundation
- Cancer Research UK [C348/A12076]
- Oxford Comprehensive Biomedical Research Centre
- EU FP7 CHIBCHA grant
- Oxford [090532/Z/09/Z]
- European Union (FP7) [258236]
- FP7 collaborative project SYSCOL in the UK
- FP7 collaborative project COST Action in the UK [BM1206]
- National Cancer Institute, National Institutes of Health [UM1 CA167551, U01 CA122839, R01 CA143237]
- Cancer Research UK [20240, 15116, 12076, 16459, 13154] Funding Source: researchfish
- Medical Research Council [MC_PC_U127527198, MC_UU_12023/3, G0701770, MC_UU_12023/20, MC_U122861325, MR/K018647/1] Funding Source: researchfish
- Tenovus Cancer Care [PhD2009/L27] Funding Source: researchfish
- MRC [MC_U122861325, MR/K018647/1, G1001799, G0701770, MC_UU_12023/3, MR/N01104X/1, MC_PC_U127527198] Funding Source: UKRI
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Genome-wide association studies (GWAS) of colorectal cancer (CRC) have identified 23 susceptibility loci thus far. Analyses of previously conducted GWAS indicate additional risk loci are yet to be discovered. To identify novel CRC susceptibility loci, we conducted a new GWAS and performed a meta-analysis with five published GWAS (totalling 7,577 cases and 9,979 controls of European ancestry), imputing genotypes utilising the 1000 Genomes Project. The combined analysis identified new, significant associations with CRC at 1p36.2 marked by rs72647484 (minor allele frequency [MAF] = 0.09) near CDC42 and WNT4 (P = 1.21 x 10(-8), odds ratio [OR] = 1.21) and at 16q24.1 marked by rs16941835 (MAF = 0.21, P = 5.06 x 10(-8); OR = 1.15) within the long non-coding RNA (lncRNA) RP11-58A18.1 and similar to 500 kb from the nearest coding gene FOXL1. Additionally we identified a promising association at 10p13 with rs10904849 intronic to CUBN (MAF = 0.32, P = 7.01 x 10(-8); OR = 1.14). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CRC. Additionally, our analysis further demonstrates that imputation can be used to exploit GWAS data to identify novel disease-causing variants.
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