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.
authors.affiliation: Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Whiffin
authors.forename: Sara E
authors.initials: SE
authors.lastname: Dobbins
authors.forename: Fay J
authors.initials: FJ
authors.lastname: Hosking
authors.forename: Claire
authors.initials: C
authors.lastname: Palles
authors.forename: Albert
authors.initials: A
authors.lastname: Tenesa
authors.forename: Yufei
authors.initials: Y
authors.lastname: Wang
authors.forename: Susan M
authors.initials: SM
authors.lastname: Farrington
authors.forename: Angela M
authors.initials: AM
authors.lastname: Jones
authors.forename: Peter
authors.initials: P
authors.lastname: Broderick
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.forename: David V
authors.initials: DV
authors.lastname: Conti
authors.forename: Fred
authors.initials: F
authors.lastname: Schumacher
authors.forename: Steve
authors.initials: S
authors.lastname: Gallinger
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.forename: John
authors.initials: J
authors.lastname: Hopper
authors.forename: Mark
authors.initials: M
authors.lastname: Jenkins
authors.forename: Malcolm G
authors.initials: MG
authors.lastname: Dunlop
authors.forename: Ian P
authors.initials: IP
authors.lastname: Tomlinson
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D002874:Chromosome Mapping; D015179:Colorectal Neoplasms / Q000235:genetics*; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D019683:Penetrance; D020641:Polymorphism, Single Nucleotide
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