Genome-wide asociation study and meta-analysis in Northrn European populations replicate multiple colorectal cancer risk loci: GWAS and meta-analysis of CRC

Tomas Tanskanen; Linda M van den Berg; Niko Välimäki; Mervi Aavikko; Eivind Ness-Jensen; Kristian Hveem; Yvonne Wettergen; Elinor Bexe Lindskog; Neeme Tonisson; Andres Metspalu; Kaisa Silander; Giulia Orlando; Philip J Law; Sari Tuupanen; Alexandra Gylfe; Ulrika A. Hanninen; Tatiana Cajuso; Johanna Kondelin; Antti-Pekka Sarin; Eero Pukkala; Pekka Jousilahti; Veikko Salomaa; Samuli Ripatti; Aarno Palotie; Heikki Järvinen; Laura Renkonen-Sinisalo; Anna Lepisto; Jan Bohm; Jukka-Pekka Mecklin; Nada A. Al-Tassan; Claire Palles; Lynn Martin; E. Barclay; Albert Tenesa; Susan Farrington; Maria Timofeeva; Brian F. Meyer; Salma M. Wakil; Harry Campbell; Christopher G Smith; Shelley Idziaszczyk; Timothy Maughan; Richard Kaplan; Rachel Kerr; David Kerr; Daniel D. Buchanan; Aung K. Win; John L Hopper; Mark C Jenkins; Polly Newcomb; Steve Gallinger; David Conti; Fred Schumacher; Graham Casey; Jeremy P Cheadle; Malcolm Dunlop; Ian P M Tomlinson; Richard S Houlston; Kimmo Palin; Lauri A Aaltonen

doi:10.1002/ijc.31076

Genome-wide asociation study and meta-analysis in Northrn European populations replicate multiple colorectal cancer risk loci: GWAS and meta-analysis of CRC

Tomas Tanskanen, Linda M van den Berg, Niko Välimäki, Mervi Aavikko, Eivind Ness-Jensen, Kristian Hveem, Yvonne Wettergen, Elinor Bexe Lindskog, Neeme Tonisson, Andres Metspalu, Kaisa Silander, Giulia Orlando, Philip J Law, Sari Tuupanen, Alexandra Gylfe, Ulrika A. Hanninen, Tatiana Cajuso, Johanna Kondelin, Antti-Pekka Sarin, Eero PukkalaPekka Jousilahti, Veikko Salomaa, Samuli Ripatti, Aarno Palotie, Heikki Järvinen, Laura Renkonen-Sinisalo, Anna Lepisto, Jan Bohm, Jukka-Pekka Mecklin, Nada A. Al-Tassan, Claire Palles, Lynn Martin, E. Barclay, Albert Tenesa, Susan Farrington, Maria Timofeeva, Brian F. Meyer, Salma M. Wakil, Harry Campbell, Christopher G Smith, Shelley Idziaszczyk, Timothy Maughan, Richard Kaplan, Rachel Kerr, David Kerr, Daniel D. Buchanan, Aung K. Win, John L Hopper, Mark C Jenkins, Polly Newcomb, Steve Gallinger, David Conti, Fred Schumacher, Graham Casey, Jeremy P Cheadle, Malcolm Dunlop, Ian P M Tomlinson, Richard S Houlston, Kimmo Palin, Lauri A Aaltonen

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

Abstract

Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer, but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 colorectal cancer cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism rs992157 (2q35) and colorectal cancer was independently replicated (p=2.08x10-4; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50x10-9; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3, and 20q13.33 were associated with colorectal cancer in the Finnish population (false discovery rate <0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of colorectal cancer and identify shared risk alleles between the Finnish population isolate and outbred populations.

Original language	English
Pages (from-to)	540-546
Journal	International Journal of Cancer
Volume	142
Issue number	3
Early online date	28 Sept 2017
DOIs	https://doi.org/10.1002/ijc.31076
Publication status	Published - 28 Sept 2017

Keywords / Materials (for Non-textual outputs)

colorectal cancer
genetic predisposition to disease
genome-wide association study
single-nucleotide polymorphism

Access to Document

10.1002/ijc.31076

Genome-wide association study and meta-analysisAccepted author manuscript, 510 KB

Integrative Genomics in Colorectal Cancer Susceptibility:Developing risk reducing interventions through understanding biology
Dunlop, M. (Principal Investigator), Campbell, H. (Co-investigator), Farrington, S. (Co-investigator) & Theodoratou, E. (Co-investigator)
UK-based charities
1/01/16 → 31/05/21
Project: Research
Elucidating the Mechanism by Which the SHROOM2 Locus on Xp22.2 Contributes to Colorectal Cancer Aetiology
Farrington, S. (Principal Investigator)
MRC
1/10/13 → 30/09/16
Project: Research

Cite this

Tanskanen, T., van den Berg, L. M., Välimäki, N., Aavikko, M., Ness-Jensen, E., Hveem, K., Wettergen, Y., Bexe Lindskog, E., Tonisson, N., Metspalu, A., Silander, K., Orlando, G., Law, P. J., Tuupanen, S., Gylfe, A., Hanninen, U. A., Cajuso, T., Kondelin, J., Sarin, A.-P., ... Aaltonen, L. A. (2017). Genome-wide asociation study and meta-analysis in Northrn European populations replicate multiple colorectal cancer risk loci: GWAS and meta-analysis of CRC. International Journal of Cancer, 142(3), 540-546. https://doi.org/10.1002/ijc.31076

@article{baf67ff5869b43799197af7b0ca807fa,

title = "Genome-wide asociation study and meta-analysis in Northrn European populations replicate multiple colorectal cancer risk loci: GWAS and meta-analysis of CRC",

abstract = "Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer, but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 colorectal cancer cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism rs992157 (2q35) and colorectal cancer was independently replicated (p=2.08x10-4; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50x10-9; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3, and 20q13.33 were associated with colorectal cancer in the Finnish population (false discovery rate <0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of colorectal cancer and identify shared risk alleles between the Finnish population isolate and outbred populations.",

keywords = "colorectal cancer, genetic predisposition to disease , genome-wide association study, single-nucleotide polymorphism",

author = "Tomas Tanskanen and {van den Berg}, {Linda M} and Niko V{\"a}lim{\"a}ki and Mervi Aavikko and Eivind Ness-Jensen and Kristian Hveem and Yvonne Wettergen and {Bexe Lindskog}, Elinor and Neeme Tonisson and Andres Metspalu and Kaisa Silander and Giulia Orlando and Law, {Philip J} and Sari Tuupanen and Alexandra Gylfe and Hanninen, {Ulrika A.} and Tatiana Cajuso and Johanna Kondelin and Antti-Pekka Sarin and Eero Pukkala and Pekka Jousilahti and Veikko Salomaa and Samuli Ripatti and Aarno Palotie and Heikki J{\"a}rvinen and Laura Renkonen-Sinisalo and Anna Lepisto and Jan Bohm and Jukka-Pekka Mecklin and Al-Tassan, {Nada A.} and Claire Palles and Lynn Martin and E. Barclay and Albert Tenesa and Susan Farrington and Maria Timofeeva and Meyer, {Brian F.} and Wakil, {Salma M.} and Harry Campbell and Smith, {Christopher G} and Shelley Idziaszczyk and Timothy Maughan and Richard Kaplan and Rachel Kerr and David Kerr and Buchanan, {Daniel D.} and Win, {Aung K.} and Hopper, {John L} and Jenkins, {Mark C} and Polly Newcomb and Steve Gallinger and David Conti and Fred Schumacher and Graham Casey and Cheadle, {Jeremy P} and Malcolm Dunlop and Tomlinson, {Ian P M} and Houlston, {Richard S} and Kimmo Palin and Aaltonen, {Lauri A}",

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journal = "International Journal of Cancer",

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Tanskanen, T, van den Berg, LM, Välimäki, N, Aavikko, M, Ness-Jensen, E, Hveem, K, Wettergen, Y, Bexe Lindskog, E, Tonisson, N, Metspalu, A, Silander, K, Orlando, G, Law, PJ, Tuupanen, S, Gylfe, A, Hanninen, UA, Cajuso, T, Kondelin, J, Sarin, A-P, Pukkala, E, Jousilahti, P, Salomaa, V, Ripatti, S, Palotie, A, Järvinen, H, Renkonen-Sinisalo, L, Lepisto, A, Bohm, J, Mecklin, J-P, Al-Tassan, NA, Palles, C, Martin, L, Barclay, E, Tenesa, A , Farrington, S, Timofeeva, M, Meyer, BF, Wakil, SM, Campbell, H, Smith, CG, Idziaszczyk, S, Maughan, T, Kaplan, R, Kerr, R, Kerr, D, Buchanan, DD, Win, AK, Hopper, JL, Jenkins, MC, Newcomb, P, Gallinger, S, Conti, D, Schumacher, F, Casey, G, Cheadle, JP, Dunlop, M, Tomlinson, IPM, Houlston, RS, Palin, K & Aaltonen, LA 2017, 'Genome-wide asociation study and meta-analysis in Northrn European populations replicate multiple colorectal cancer risk loci: GWAS and meta-analysis of CRC', International Journal of Cancer, vol. 142, no. 3, pp. 540-546. https://doi.org/10.1002/ijc.31076

Genome-wide asociation study and meta-analysis in Northrn European populations replicate multiple colorectal cancer risk loci: GWAS and meta-analysis of CRC. / Tanskanen, Tomas; van den Berg, Linda M; Välimäki, Niko et al.
In: International Journal of Cancer, Vol. 142, No. 3, 28.09.2017, p. 540-546.

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

TY - JOUR

T1 - Genome-wide asociation study and meta-analysis in Northrn European populations replicate multiple colorectal cancer risk loci

T2 - GWAS and meta-analysis of CRC

AU - Tanskanen, Tomas

AU - van den Berg, Linda M

AU - Välimäki, Niko

AU - Aavikko, Mervi

AU - Ness-Jensen, Eivind

AU - Hveem, Kristian

AU - Wettergen, Yvonne

AU - Bexe Lindskog, Elinor

AU - Tonisson, Neeme

AU - Metspalu, Andres

AU - Silander, Kaisa

AU - Orlando, Giulia

AU - Law, Philip J

AU - Tuupanen, Sari

AU - Gylfe, Alexandra

AU - Hanninen, Ulrika A.

AU - Cajuso, Tatiana

AU - Kondelin, Johanna

AU - Sarin, Antti-Pekka

AU - Pukkala, Eero

AU - Jousilahti, Pekka

AU - Salomaa, Veikko

AU - Ripatti, Samuli

AU - Palotie, Aarno

AU - Järvinen, Heikki

AU - Renkonen-Sinisalo, Laura

AU - Lepisto, Anna

AU - Bohm, Jan

AU - Mecklin, Jukka-Pekka

AU - Al-Tassan, Nada A.

AU - Palles, Claire

AU - Martin, Lynn

AU - Barclay, E.

AU - Tenesa, Albert

AU - Farrington, Susan

AU - Timofeeva, Maria

AU - Meyer, Brian F.

AU - Wakil, Salma M.

AU - Campbell, Harry

AU - Smith, Christopher G

AU - Idziaszczyk, Shelley

AU - Maughan, Timothy

AU - Kaplan, Richard

AU - Kerr, Rachel

AU - Kerr, David

AU - Buchanan, Daniel D.

AU - Win, Aung K.

AU - Hopper, John L

AU - Jenkins, Mark C

AU - Newcomb, Polly

AU - Gallinger, Steve

AU - Conti, David

AU - Schumacher, Fred

AU - Casey, Graham

AU - Cheadle, Jeremy P

AU - Dunlop, Malcolm

AU - Tomlinson, Ian P M

AU - Houlston, Richard S

AU - Palin, Kimmo

AU - Aaltonen, Lauri A

PY - 2017/9/28

Y1 - 2017/9/28

N2 - Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer, but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 colorectal cancer cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism rs992157 (2q35) and colorectal cancer was independently replicated (p=2.08x10-4; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50x10-9; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3, and 20q13.33 were associated with colorectal cancer in the Finnish population (false discovery rate <0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of colorectal cancer and identify shared risk alleles between the Finnish population isolate and outbred populations.

AB - Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer, but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 colorectal cancer cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism rs992157 (2q35) and colorectal cancer was independently replicated (p=2.08x10-4; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50x10-9; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3, and 20q13.33 were associated with colorectal cancer in the Finnish population (false discovery rate <0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of colorectal cancer and identify shared risk alleles between the Finnish population isolate and outbred populations.

KW - colorectal cancer

KW - genetic predisposition to disease

KW - genome-wide association study

KW - single-nucleotide polymorphism

U2 - 10.1002/ijc.31076

DO - 10.1002/ijc.31076

M3 - Article

SN - 0020-7136

VL - 142

SP - 540

EP - 546

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 3

ER -

Genome-wide asociation study and meta-analysis in Northrn European populations replicate multiple colorectal cancer risk loci: GWAS and meta-analysis of CRC

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

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Projects

Integrative Genomics in Colorectal Cancer Susceptibility:Developing risk reducing interventions through understanding biology

Elucidating the Mechanism by Which the SHROOM2 Locus on Xp22.2 Contributes to Colorectal Cancer Aetiology

Cite this