@article{bb08b4bb8d2340fb9c7487dd508c5851,
title = "A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer",
abstract = "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=1.21×10-8, odds ratio [OR]=1.21) and at 16q24.1 marked by rs16941835 (MAF=0.21, P=5.06×10-8; OR=1.15) within the long non-coding RNA (lncRNA) RP11-58A18.1 and ∼500kb from the nearest coding gene FOXL1. Additionally we identified a promising association at 10p13 with rs10904849 intronic to CUBN (MAF=0.32, P=7.01×10-8; 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.",
author = "Al-Tassan, {Nada A.} and Nicola Whiffin and Hosking, {Fay J.} and Claire Palles and Farrington, {Susan M.} and Dobbins, {Sara E.} and Rebecca Harris and Maggie Gorman and Albert Tenesa and Meyer, {Brian F.} and Wakil, {Salma M.} and Ben Kinnersley and Harry Campbell and Lynn Martin and Smith, {Christopher G.} and Shelley Idziaszczyk and Ella Barclay and Maughan, {Timothy S.} and Richard Kaplan and Rachel Kerr and David Kerr and Buchannan, {Daniel D.} and {Ko Win}, Aung and John Hopper and Mark Jenkins and Lindor, {Noralane M.} and Newcomb, {Polly A.} and Steve Gallinger and David Conti and Fred Schumacher and Graham Casey and Dunlop, {Malcolm G.} and Tomlinson, {Ian P.} and Cheadle, {Jeremy P.} and Houlston, {Richard S.}",
note = "Funding Information: The COIN and COIN-B trials were funded by Cancer Research UK and the Medical Research Council and were conducted with the support of the National Institute of Health Research Cancer Research Network. COIN and COIN-B translational studies were supported by the Bobby Moore Fund from Cancer Research UK, Tenovus, the Kidani Trust, Cancer Research Wales and the National Institute for Social Care and Health Research Cancer Genetics Biomedical Research Unit (2011–2014) (all awarded to J.P.C.). We thank the patients and their families who participated in COIN and COIN-B, and gave their consent for this research, and the investigators and pathologists throughout the UK who submitted samples for assessment. N.A.A., B.F.M. and S.M.W. were funded and supported by KFSHRC. At the Institute of Cancer Research, the work was supported by Cancer Research UK (C1298/A8362 - Bobby Moore Fund for Cancer Research UK). Additional support was provided by the National Cancer Research Network and the NHS via the Biological Research Centre of the National Institute for Health Research at the Royal Marsden Hospital NHS Trust. N.W. and B.K. were in receipt of PhD studentships from the ICR. B.K additionally receives funding from the Sir John Fisher Foundation. In Edinburgh the work was supported by Programme Grant funding from Cancer Research UK (C348/A12076). In Oxford additional funding was provided by the Oxford Comprehensive Biomedical Research Centre (C.P. and I.P.M.T.) and the EU FP7 CHIBCHA grant (I.P.M.T.). Core infrastructure support to the Wellcome Trust Centre for Human Genetics, Oxford was provided by grant (090532/Z/09/Z). We are grateful to many colleagues within UK Clinical Genetics Departments (for CORGI) and to many collaborators who participated in the VICTOR and QUASAR2 trials. We also thank colleagues from the UK National Cancer Research Network (for NSCCG). Support from the European Union (FP7/207-2013) under grant 258236 and FP7 collaborative project SYSCOL and COST Action BM1206 in the UK is also acknowledged. The work of the Colon Cancer Family Registry CFR was supported by grant UM1 CA167551 from the National Cancer Institute, National Institutes of Health and through cooperative agreements with members of the Colon CFR and Principal Investigators. Collaborating centers include the Australasian Colorectal Cancer Family Registry (U01/U24 CA097735), the USC Colorectal Cancer Family Registry (U01/U24 CA074799), Mayo Clinic Cooperative Familial Registry for Colon Cancer Studies (U01/U24 CA074800), Ontario Registry for Studies of Familial Colorectal Cancer (U01/U24 CA074783), the Seattle Colorectal Cancer Family Registry (U01/U24 CA074794), and the University of Hawaii Colorectal Cancer Family Registry (U01/U24 CA074806). The Colon CFR GWAS was supported by funding from the National Cancer Institute, National Institutes of Health (U01 CA122839 and R01 CA143237 to GC). This study made use of genotyping data from the 1958 Birth Cohort, kindly made available by the Wellcome Trust Case Control Consortium 2. A full list of the investigators who contributed to the generation of the data is available at http://www.wtccc.org.uk/. The results published here are in whole or part based upon data generated by The Cancer Genome Atlas pilot project established by the NCI and NHGRI. Information about TCGA and the investigators and institutions which constitute the TCGA research network can be found at http://cancergenome.nih.gov/. Finally, we would like to thank all individuals who participated in the study.",
year = "2015",
month = may,
day = "20",
doi = "10.1038/srep10442",
language = "English (US)",
volume = "5",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}