@article{425925a2fa6246bb88d3a0d1e88d2d4e,
title = "Deciphering the genetic architecture of low-penetrance susceptibility to colorectal cancer",
abstract = "Recent genome-wide association studies (GWASs) have identified common variants at 16 autosomal regions influencing the risk of developing colorectal cancer (CRC). To decipher the genetic basis of the association signals at these loci, we performed a meta-analysis of data from five GWASs, totalling 5626 cases and 7817 controls, using imputation to recover un-typed genotypes. To enhance our ability to discover low-frequency risk variants, in addition to using 1000 Genomes Project data as a reference panel, we made use of high-coverage sequencing data on 253 individuals, 199 with early-onset familial CRC. For 13 of the regions, it was possible to refine the association signal identifying a smaller region of interest likely to harbour the functional variant. Our analysis did not provide evidence that any of the associations at the 16 loci being a consequence of synthetic associations rather than linkage disequilibrium with a common risk variant.",
author = "Nicola Whiffin and Dobbins, {Sara E.} and Hosking, {Fay J.} and Claire Palles and Albert Tenesa and Yufei Wang and Farrington, {Susan M.} and Jones, {Angela M.} and Peter Broderick and Harry Campbell and Newcomb, {Polly A.} and Graham Casey and Conti, {David V.} and Fred Schumacher and Steve Gallinger and Lindor, {Noralane M.} and John Hopper and Mark Jenkins and Dunlop, {Malcolm G.} and Tomlinson, {Ian P.} and Houlston, {Richard S.}",
note = "Funding Information: In Oxford, additional funding was provided by the Oxford Comprehensive Biomedical Research Centre (C.P. and I.P.T.) and the European Union Framework Programme 7 (FP7) CHIBCHA grant (A.M.J. and I.P.T.). Core infrastructure support to the Wellcome Trust Centre for Human Genetics, Oxford, was provided by grant (090532/Z/09/Z). Funding Information: Research was also funded by the European Union FP7 (FP7/ 207-2013) under grant 258236, FP7 collaborative project SYSCOL. Funding Information: In Edinburgh, funding was provided by a Cancer Research UK Programme Grant (C348/A12076) and a Centre Grant from the CORE Charity. Lothian Birth Cohort Illumina genotyping was supported by the UK Biotechnology and Biological Sciences Research Council (BBSRC). Phenotype collection in the Lothian Birth Cohort 1921 was supported by the BBSRC, The Royal Society and The Chief Scientist Office of the Scottish Government. Phenotype collection in the Lothian Birth Cohort 1936 was supported by Research into Ageing (continues as part of Age UK{\textquoteright}s The Disconnected Mind project). The work on the Lothian Birth Cohorts was undertaken at the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative (G0700704/84698). Funding from the BBSRC, EPSRC, ESRC and MRC is gratefully acknowledged. Funding Information: Cancer Research UK provided principal funding for this study individually to R.S.H. (C1298/A8362 – Bobby Moore Fund for Cancer Research UK), I.P.T. and M.G.D. At the Institute of Cancer Research, additional funding was provided by a Centre Grant from Core as part of the Digestive Cancer Campaign, the National Cancer Research Network and the NHS via the Biological Research Centre of the NIHR at the Royal Marsden Hospital NHS Trust. N.W. received a PhD studentship from the Institute of Cancer Research. We are grateful to many colleagues within the 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). Funding Information: This work of the Colon Cancer Family Registry (CFR) was supported by the US National Cancer Institute, National Institutes of Health (CA-95-011), and through cooperative agreements with members of the Colon CFR and Principal Investigators. Collaborating centres include the Australasian Colorectal Cancer Family Registry (U01 CA097735), the Familial Colorectal Neoplasia Collaborative Group (U01 CA074799), the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783) and the Seattle Colorectal Cancer Family Registry (U01 CA074794). The Colon CFR GWAS was supported by funding from the US National Cancer Institute, National Institutes of Health (U01CA122839 to G.C.).",
year = "2013",
month = dec,
doi = "10.1093/hmg/ddt357",
language = "English (US)",
volume = "22",
pages = "5075--5082",
journal = "Human molecular genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "24",
}