Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A

Hansong Wang; Terrilea Burnett; Suminori Kono; Christopher A. Haiman; Motoki Iwasaki; Lynne R. Wilkens; Lenora W.M. Loo; David Van Den Berg; Laurence N. Kolonel; Brian E. Henderson; Temitope O. Keku; Robert S. Sandler; Lisa B. Signorello; William J. Blot; Polly A. Newcomb; Mala Pande; Christopher I. Amos; Dee W. West; Stéphane Bézieau; Sonja I. Berndt; Brent W. Zanke; Li Hsu; Noralane M. Lindor; Robert W. Haile; John L. Hopper; Mark A. Jenkins; Steven Gallinger; Graham Casey; Stephanie L. Stenzel; Fredrick R. Schumacher; Ulrike Peters; Stephen B. Gruber; Shoichiro Tsugane; Daniel O. Stram; Loïc Le Marchand

doi:10.1038/ncomms5613

Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A

Hansong Wang, Terrilea Burnett, Suminori Kono, Christopher A. Haiman, Motoki Iwasaki, Lynne R. Wilkens, Lenora W.M. Loo, David Van Den Berg, Laurence N. Kolonel, Brian E. Henderson, Temitope O. Keku, Robert S. Sandler, Lisa B. Signorello, William J. Blot, Polly A. Newcomb, Mala Pande, Christopher I. Amos, Dee W. West, Stéphane Bézieau, Sonja I. BerndtBrent W. Zanke, Li Hsu, Noralane M. Lindor, Robert W. Haile, John L. Hopper, Mark A. Jenkins, Steven Gallinger, Graham Casey, Stephanie L. Stenzel, Fredrick R. Schumacher, Ulrike Peters, Stephen B. Gruber, Shoichiro Tsugane, Daniel O. Stram, Loïc Le Marchand

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Abstract

The genetic basis of sporadic colorectal cancer (CRC) is not well explained by known risk polymorphisms. Here we perform a meta-analysis of two genome-wide association studies in 2,627 cases and 3,797 controls of Japanese ancestry and 1,894 cases and 4,703 controls of African ancestry, to identify genetic variants that contribute to CRC susceptibility. We replicate genome-wide statistically significant associations (P<5 × 10^-8) in 16,823 cases and 18,211 controls of European ancestry. This study reveals a new pan-ethnic CRC risk locus at 10q25 (rs12241008, intronic to VTI1A; P=1.4 × 10 ^-9), providing additional insight into the aetiology of CRC and highlighting the value of association mapping in diverse populations.

Original language	English (US)
Article number	4613
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5613
State	Published - Aug 8 2014

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Wang, H., Burnett, T., Kono, S., Haiman, C. A., Iwasaki, M., Wilkens, L. R., Loo, L. W. M., Van Den Berg, D., Kolonel, L. N., Henderson, B. E., Keku, T. O., Sandler, R. S., Signorello, L. B., Blot, W. J., Newcomb, P. A., Pande, M., Amos, C. I., West, D. W., Bézieau, S., ... Le Marchand, L. (2014). Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A. Nature communications, 5, Article 4613. https://doi.org/10.1038/ncomms5613

Wang, H, Burnett, T, Kono, S, Haiman, CA, Iwasaki, M, Wilkens, LR, Loo, LWM, Van Den Berg, D, Kolonel, LN, Henderson, BE, Keku, TO, Sandler, RS, Signorello, LB, Blot, WJ, Newcomb, PA, Pande, M, Amos, CI, West, DW, Bézieau, S, Berndt, SI, Zanke, BW, Hsu, L, Lindor, NM, Haile, RW, Hopper, JL, Jenkins, MA, Gallinger, S, Casey, G, Stenzel, SL, Schumacher, FR, Peters, U, Gruber, SB, Tsugane, S, Stram, DO & Le Marchand, L 2014, 'Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A', Nature communications, vol. 5, 4613. https://doi.org/10.1038/ncomms5613

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title = "Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A",

abstract = "The genetic basis of sporadic colorectal cancer (CRC) is not well explained by known risk polymorphisms. Here we perform a meta-analysis of two genome-wide association studies in 2,627 cases and 3,797 controls of Japanese ancestry and 1,894 cases and 4,703 controls of African ancestry, to identify genetic variants that contribute to CRC susceptibility. We replicate genome-wide statistically significant associations (P<5 × 10-8) in 16,823 cases and 18,211 controls of European ancestry. This study reveals a new pan-ethnic CRC risk locus at 10q25 (rs12241008, intronic to VTI1A; P=1.4 × 10 -9), providing additional insight into the aetiology of CRC and highlighting the value of association mapping in diverse populations.",

author = "Hansong Wang and Terrilea Burnett and Suminori Kono and Haiman, {Christopher A.} and Motoki Iwasaki and Wilkens, {Lynne R.} and Loo, {Lenora W.M.} and {Van Den Berg}, David and Kolonel, {Laurence N.} and Henderson, {Brian E.} and Keku, {Temitope O.} and Sandler, {Robert S.} and Signorello, {Lisa B.} and Blot, {William J.} and Newcomb, {Polly A.} and Mala Pande and Amos, {Christopher I.} and West, {Dee W.} and St{\'e}phane B{\'e}zieau and Berndt, {Sonja I.} and Zanke, {Brent W.} and Li Hsu and Lindor, {Noralane M.} and Haile, {Robert W.} and Hopper, {John L.} and Jenkins, {Mark A.} and Steven Gallinger and Graham Casey and Stenzel, {Stephanie L.} and Schumacher, {Fredrick R.} and Ulrike Peters and Gruber, {Stephen B.} and Shoichiro Tsugane and Stram, {Daniel O.} and {Le Marchand}, Lo{\"i}c",

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AU - Wang, Hansong

AU - Burnett, Terrilea

AU - Kono, Suminori

AU - Haiman, Christopher A.

AU - Iwasaki, Motoki

AU - Wilkens, Lynne R.

AU - Loo, Lenora W.M.

AU - Van Den Berg, David

AU - Kolonel, Laurence N.

AU - Henderson, Brian E.

AU - Keku, Temitope O.

AU - Sandler, Robert S.

AU - Signorello, Lisa B.

AU - Blot, William J.

AU - Newcomb, Polly A.

AU - Pande, Mala

AU - Amos, Christopher I.

AU - West, Dee W.

AU - Bézieau, Stéphane

AU - Berndt, Sonja I.

AU - Zanke, Brent W.

AU - Hsu, Li

AU - Lindor, Noralane M.

AU - Haile, Robert W.

AU - Hopper, John L.

AU - Jenkins, Mark A.

AU - Gallinger, Steven

AU - Casey, Graham

AU - Stenzel, Stephanie L.

AU - Schumacher, Fredrick R.

AU - Peters, Ulrike

AU - Gruber, Stephen B.

AU - Tsugane, Shoichiro

AU - Stram, Daniel O.

AU - Le Marchand, Loïc

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N2 - The genetic basis of sporadic colorectal cancer (CRC) is not well explained by known risk polymorphisms. Here we perform a meta-analysis of two genome-wide association studies in 2,627 cases and 3,797 controls of Japanese ancestry and 1,894 cases and 4,703 controls of African ancestry, to identify genetic variants that contribute to CRC susceptibility. We replicate genome-wide statistically significant associations (P<5 × 10-8) in 16,823 cases and 18,211 controls of European ancestry. This study reveals a new pan-ethnic CRC risk locus at 10q25 (rs12241008, intronic to VTI1A; P=1.4 × 10 -9), providing additional insight into the aetiology of CRC and highlighting the value of association mapping in diverse populations.

AB - The genetic basis of sporadic colorectal cancer (CRC) is not well explained by known risk polymorphisms. Here we perform a meta-analysis of two genome-wide association studies in 2,627 cases and 3,797 controls of Japanese ancestry and 1,894 cases and 4,703 controls of African ancestry, to identify genetic variants that contribute to CRC susceptibility. We replicate genome-wide statistically significant associations (P<5 × 10-8) in 16,823 cases and 18,211 controls of European ancestry. This study reveals a new pan-ethnic CRC risk locus at 10q25 (rs12241008, intronic to VTI1A; P=1.4 × 10 -9), providing additional insight into the aetiology of CRC and highlighting the value of association mapping in diverse populations.

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Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A

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