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 Kerr; David Kerr; Daniel D. Buchannan; Aung Ko Win; John Hopper; Mark Jenkins; Noralane M. Lindor; Polly A. Newcomb; Steve Gallinger; David Conti; Fred Schumacher; Graham Casey; Malcolm G. Dunlop; Ian P. Tomlinson; Jeremy P. Cheadle; Richard S. Houlston

doi:10.1038/srep10442

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 M. Lindor, Polly A. Newcomb, Steve Gallinger, David Conti, Fred Schumacher, Graham Casey, Malcolm G. Dunlop, Ian P. Tomlinson, Jeremy P. Cheadle, Richard S. Houlston^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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 x 10(-8), odds ratio [OR] = 1.21) and at 16q24.1 marked by rs16941835 (MAF = 0.21, P = 5.06 x 10(-8); OR = 1.15) within the long non-coding RNA (lncRNA) RP11-58A18.1 and similar to 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 x 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.

Original language	English
Article number	10442
Number of pages	10
Journal	Scientific Reports
Volume	5
DOIs	https://doi.org/10.1038/srep10442
Publication status	Published - 20 May 2015

Keywords / Materials (for Non-textual outputs)

GENOME-WIDE ASSOCIATION
SUSCEPTIBILITY LOCI
COMMON VARIATION
COLON-CANCER
MICROSATELLITE INSTABILITY
GENETIC-VARIATION
BREAST-CANCER
LARGE-SCALE
CHEMOTHERAPY
CETUXIMAB

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10.1038/srep10442

A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer
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Al-Tassan, N. A., Whiffin, N., Hosking, F. J., Palles, C., Farrington, S. M., Dobbins, S. E., Harris, R., Gorman, M., Tenesa, A., Meyer, B. F., Wakil, S. M., Kinnersley, B., Campbell, H., Martin, L., Smith, C. G., Idziaszczyk, S., Barclay, E., Maughan, T. S., Kaplan, R., ... Houlston, R. S. (2015). A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer. Scientific Reports, 5, Article 10442. https://doi.org/10.1038/srep10442

@article{e2035e026b92455eaee2466ce09a352c,

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 x 10(-8), odds ratio [OR] = 1.21) and at 16q24.1 marked by rs16941835 (MAF = 0.21, P = 5.06 x 10(-8); OR = 1.15) within the long non-coding RNA (lncRNA) RP11-58A18.1 and similar to 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 x 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.",

keywords = "GENOME-WIDE ASSOCIATION, SUSCEPTIBILITY LOCI, COMMON VARIATION, COLON-CANCER, MICROSATELLITE INSTABILITY, GENETIC-VARIATION, BREAST-CANCER, LARGE-SCALE, CHEMOTHERAPY, CETUXIMAB",

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 Win, {Aung Ko} 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 = "Date of Acceptance: 13/04/2015",

year = "2015",

month = may,

day = "20",

doi = "10.1038/srep10442",

language = "English",

volume = "5",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

}

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, Win, AK, 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

TY - JOUR

T1 - A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer

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 - Win, Aung Ko

AU - Hopper, John

AU - Jenkins, Mark

AU - Lindor, Noralane M.

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.

N1 - Date of Acceptance: 13/04/2015

PY - 2015/5/20

Y1 - 2015/5/20

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 x 10(-8), odds ratio [OR] = 1.21) and at 16q24.1 marked by rs16941835 (MAF = 0.21, P = 5.06 x 10(-8); OR = 1.15) within the long non-coding RNA (lncRNA) RP11-58A18.1 and similar to 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 x 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.

AB - 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 x 10(-8), odds ratio [OR] = 1.21) and at 16q24.1 marked by rs16941835 (MAF = 0.21, P = 5.06 x 10(-8); OR = 1.15) within the long non-coding RNA (lncRNA) RP11-58A18.1 and similar to 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 x 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.

KW - GENOME-WIDE ASSOCIATION

KW - SUSCEPTIBILITY LOCI

KW - COMMON VARIATION

KW - COLON-CANCER

KW - MICROSATELLITE INSTABILITY

KW - GENETIC-VARIATION

KW - BREAST-CANCER

KW - LARGE-SCALE

KW - CHEMOTHERAPY

KW - CETUXIMAB

U2 - 10.1038/srep10442

DO - 10.1038/srep10442

M3 - Article

SN - 2045-2322

VL - 5

JO - Scientific Reports

JF - Scientific Reports

M1 - 10442

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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