A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer

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

Research output: Contribution to journalArticle

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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<sup>-8</sup>, odds ratio [OR]=1.21) and at 16q24.1 marked by rs16941835 (MAF=0.21, P=5.06×10<sup>-8</sup>; 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<sup>-8</sup>; 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.

Original languageEnglish (US)
Article number10442
JournalScientific Reports
Volume5
DOIs
StatePublished - May 20 2015

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Genome-Wide Association Study
Meta-Analysis
Colorectal Neoplasms
Gene Frequency
Odds Ratio
Long Noncoding RNA
Genetic Predisposition to Disease
Genotype
Genome
Genes

ASJC Scopus subject areas

  • General

Cite this

Al-Tassan, N. A., Whiffin, N., Hosking, F. J., Palles, C., Farrington, S. M., Dobbins, S. E., ... Houlston, R. S. (2015). A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer. Scientific Reports, 5, [10442]. https://doi.org/10.1038/srep10442

A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer. / 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; Buchannan, Daniel D.; Ko Win, Aung; Hopper, John; Jenkins, Mark; Lindor, Noralane Morey; Newcomb, Polly A.; Gallinger, Steve; Conti, David; Schumacher, Fred; Casey, Graham; Dunlop, Malcolm G.; Tomlinson, Ian P.; Cheadle, Jeremy P.; Houlston, Richard S.

In: Scientific Reports, Vol. 5, 10442, 20.05.2015.

Research output: Contribution to journalArticle

Al-Tassan, NA, Whiffin, N, Hosking, FJ, Palles, C, Farrington, SM, Dobbins, SE, Harris, R, Gorman, M, Tenesa, A, Meyer, BF, Wakil, SM, Kinnersley, B, Campbell, H, Martin, L, Smith, CG, Idziaszczyk, S, Barclay, E, Maughan, TS, Kaplan, R, Kerr, R, Kerr, D, Buchannan, DD, Ko Win, A, Hopper, J, Jenkins, M, Lindor, NM, Newcomb, PA, Gallinger, S, Conti, D, Schumacher, F, Casey, G, Dunlop, MG, Tomlinson, IP, Cheadle, JP & Houlston, RS 2015, 'A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer', Scientific Reports, vol. 5, 10442. https://doi.org/10.1038/srep10442
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 ; Buchannan, Daniel D. ; Ko Win, Aung ; Hopper, John ; Jenkins, Mark ; Lindor, Noralane Morey ; Newcomb, Polly A. ; Gallinger, Steve ; Conti, David ; Schumacher, Fred ; Casey, Graham ; Dunlop, Malcolm G. ; Tomlinson, Ian P. ; Cheadle, Jeremy P. ; Houlston, Richard S. / A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer. In: Scientific Reports. 2015 ; Vol. 5.
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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.",
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AU - Al-Tassan, Nada A.

AU - Whiffin, Nicola

AU - Hosking, Fay J.

AU - Palles, Claire

AU - Farrington, Susan M.

AU - Dobbins, Sara E.

AU - Harris, Rebecca

AU - Gorman, Maggie

AU - Tenesa, Albert

AU - Meyer, Brian F.

AU - Wakil, Salma M.

AU - Kinnersley, Ben

AU - Campbell, Harry

AU - Martin, Lynn

AU - Smith, Christopher G.

AU - Idziaszczyk, Shelley

AU - Barclay, Ella

AU - Maughan, Timothy S.

AU - Kaplan, Richard

AU - Kerr, Rachel

AU - Kerr, David

AU - Buchannan, Daniel D.

AU - Ko Win, Aung

AU - Hopper, John

AU - Jenkins, Mark

AU - Lindor, Noralane Morey

AU - Newcomb, Polly A.

AU - Gallinger, Steve

AU - Conti, David

AU - Schumacher, Fred

AU - Casey, Graham

AU - Dunlop, Malcolm G.

AU - Tomlinson, Ian P.

AU - Cheadle, Jeremy P.

AU - Houlston, Richard S.

PY - 2015/5/20

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N2 - 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.

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