Author:
Al-Tassan Nada A.,Whiffin Nicola,Hosking Fay J.,Palles Claire,Farrington Susan M.,Dobbins Sara E.,Harris Rebecca,Gorman Maggie,Tenesa Albert,Meyer Brian F.,Wakil Salma M.,Kinnersley Ben,Campbell Harry,Martin Lynn,Smith Christopher G.,Idziaszczyk Shelley,Barclay Ella,Maughan Timothy S.,Kaplan Richard,Kerr Rachel,Kerr David,Buchanan Daniel D.,Win Aung Ko,Hopper John,Jenkins Mark,Lindor Noralane M.,Newcomb Polly A.,Gallinger Steve,Conti David,Schumacher Fred,Casey Graham,Dunlop Malcolm G.,Tomlinson Ian P.,Cheadle Jeremy P.,Houlston Richard S.
Abstract
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 ~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 × 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.
Publisher
Springer Science and Business Media LLC