Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer

Thorunn Rafnar; Patrick Sulem; Gudmar Thorleifsson; Sita H. Vermeulen; Hannes Helgason; Jona Saemundsdottir; Sigurjon A. Gudjonsson; Asgeir Sigurdsson; Simon N. Stacey; Julius Gudmundsson; Hrefna Johannsdottir; Kristin Alexiusdottir; Vigdis Petursdottir; Sigfus Nikulasson; Gudmundur Geirsson; Thorvaldur Jonsson; Katja K.H. Aben; Anne J. Grotenhuis; Gerald W. Verhaegh; Aleksandra M. Dudek; J. Alfred Witjes; Antoine G. van der Heijden; Alina Vrieling; Tessel E. Galesloot; Ana De Juan; Angeles Panadero; Fernando Rivera; Carolyn Hurst; D. Timothy Bishop; Sei C. Sak; Ananya Choudhury; Mark T.W. Teo; Cecilia Arici; Angela Carta; Elena Toninelli; Petra de Verdier; Peter Rudnai; Eugene Gurzau; Kvetoslava Koppova; Kirstin A. van der Keur; Irene Lurkin; Mieke Goossens; Eliane Kellen; Simonetta Guarrera; Alessia Russo; Rossana Critelli; Carlotta Sacerdote; Paolo Vineis; Clémentine Krucker; Maurice P. Zeegers; Holger Gerullis; Daniel Ovsiannikov; Frank Volkert; Jan G. Hengstler; Silvia Selinski; Olafur T. Magnusson; Gisli Masson; Augustine Kong; Daniel Gudbjartsson; Annika Lindblom; Ellen Zwarthoff; Stefano Porru; Klaus Golka; Frank Buntinx; Giuseppe Matullo; Rajiv Kumar; José I. Mayordomo; D. Gunnar Steineck; Anne E. Kiltie; Eirikur Jonsson; François Radvanyi; Margaret A. Knowles; Unnur Thorsteinsdottir; Lambertus A. Kiemeney; Kari Stefansson

doi:10.1093/hmg/ddu264

Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer

Thorunn Rafnar
, Patrick Sulem
, Gudmar Thorleifsson
, Sita H. Vermeulen
, Hannes Helgason
, Jona Saemundsdottir
, Sigurjon A. Gudjonsson
, Asgeir Sigurdsson
, Simon N. Stacey
, Julius Gudmundsson
, Hrefna Johannsdottir
, Kristin Alexiusdottir
, Vigdis Petursdottir
, Sigfus Nikulasson
, Gudmundur Geirsson
, Thorvaldur Jonsson
, Katja K.H. Aben
, Anne J. Grotenhuis
, Gerald W. Verhaegh
, Aleksandra M. Dudek

J. Alfred Witjes, Antoine G. van der Heijden, Alina Vrieling, Tessel E. Galesloot, Ana De Juan, Angeles Panadero, Fernando Rivera, Carolyn Hurst, D. Timothy Bishop, Sei C. Sak, Ananya Choudhury, Mark T.W. Teo, Cecilia Arici, Angela Carta, Elena Toninelli, Petra de Verdier, Peter Rudnai, Eugene Gurzau, Kvetoslava Koppova, Kirstin A. van der Keur, Irene Lurkin, Mieke Goossens, Eliane Kellen, Simonetta Guarrera, Alessia Russo, Rossana Critelli, Carlotta Sacerdote, Paolo Vineis, Clémentine Krucker, Maurice P. Zeegers, Holger Gerullis, Daniel Ovsiannikov, Frank Volkert, Jan G. Hengstler, Silvia Selinski, Olafur T. Magnusson, Gisli Masson, Augustine Kong, Daniel Gudbjartsson, Annika Lindblom, Ellen Zwarthoff, Stefano Porru, Klaus Golka, Frank Buntinx, Giuseppe Matullo, Rajiv Kumar, José I. Mayordomo, D. Gunnar Steineck, Anne E. Kiltie, Eirikur Jonsson, François Radvanyi, Margaret A. Knowles, Unnur Thorsteinsdottir, Lambertus A. Kiemeney, Kari Stefansson

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

Abstract

Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC cases and 10 456 controls. We tested a dataset containing 34.2 million variants, generated by imputation based on whole-genome sequencing of 2230 Icelanders. Several correlated variants at 20p12, represented by rs62185668, show genome-wide significant association with UBC after combining discovery and replication results (OR = 1.19, P = 1.5 × 10^-11 for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately kb upstream from the JAG1 gene, an important component of the Notch signaling pathways that may be oncogenic or tumor suppressive in several forms of cancer. Our results add to the growing number of UBC risk variants discovered through GWAS.

Original language	English
Pages (from-to)	5545-5557
Number of pages	13
Journal	Human Molecular Genetics
Volume	23
Issue number	20
DOIs	https://doi.org/10.1093/hmg/ddu264
Publication status	Published - 15 Nov 2014
Externally published	Yes

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SDG 3 Good Health and Well-being

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10.1093/hmg/ddu264

Cite this

Rafnar, T., Sulem, P., Thorleifsson, G., Vermeulen, S. H., Helgason, H., Saemundsdottir, J., Gudjonsson, S. A., Sigurdsson, A., Stacey, S. N., Gudmundsson, J., Johannsdottir, H., Alexiusdottir, K., Petursdottir, V., Nikulasson, S., Geirsson, G., Jonsson, T., Aben, K. K. H., Grotenhuis, A. J., Verhaegh, G. W., ... Stefansson, K. (2014). Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer. Human Molecular Genetics, 23(20), 5545-5557. https://doi.org/10.1093/hmg/ddu264

@article{e96a1e1220f645fd950234a64d21fe81,

title = "Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer",

abstract = "Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC cases and 10 456 controls. We tested a dataset containing 34.2 million variants, generated by imputation based on whole-genome sequencing of 2230 Icelanders. Several correlated variants at 20p12, represented by rs62185668, show genome-wide significant association with UBC after combining discovery and replication results (OR = 1.19, P = 1.5 × 10-11 for rs62185668-A, minor allele frequency = 23.6\%). The variants are located in a non-coding region approximately kb upstream from the JAG1 gene, an important component of the Notch signaling pathways that may be oncogenic or tumor suppressive in several forms of cancer. Our results add to the growing number of UBC risk variants discovered through GWAS.",

author = "Thorunn Rafnar and Patrick Sulem and Gudmar Thorleifsson and Vermeulen, \{Sita H.\} and Hannes Helgason and Jona Saemundsdottir and Gudjonsson, \{Sigurjon A.\} and Asgeir Sigurdsson and Stacey, \{Simon N.\} and Julius Gudmundsson and Hrefna Johannsdottir and Kristin Alexiusdottir and Vigdis Petursdottir and Sigfus Nikulasson and Gudmundur Geirsson and Thorvaldur Jonsson and Aben, \{Katja K.H.\} and Grotenhuis, \{Anne J.\} and Verhaegh, \{Gerald W.\} and Dudek, \{Aleksandra M.\} and \{Alfred Witjes\}, J. and \{van der Heijden\}, \{Antoine G.\} and Alina Vrieling and Galesloot, \{Tessel E.\} and \{De Juan\}, Ana and Angeles Panadero and Fernando Rivera and Carolyn Hurst and \{Timothy Bishop\}, D. and Sak, \{Sei C.\} and Ananya Choudhury and Teo, \{Mark T.W.\} and Cecilia Arici and Angela Carta and Elena Toninelli and \{de Verdier\}, Petra and Peter Rudnai and Eugene Gurzau and Kvetoslava Koppova and \{van der Keur\}, \{Kirstin A.\} and Irene Lurkin and Mieke Goossens and Eliane Kellen and Simonetta Guarrera and Alessia Russo and Rossana Critelli and Carlotta Sacerdote and Paolo Vineis and Cl{\'e}mentine Krucker and Zeegers, \{Maurice P.\} and Holger Gerullis and Daniel Ovsiannikov and Frank Volkert and Hengstler, \{Jan G.\} and Silvia Selinski and Magnusson, \{Olafur T.\} and Gisli Masson and Augustine Kong and Daniel Gudbjartsson and Annika Lindblom and Ellen Zwarthoff and Stefano Porru and Klaus Golka and Frank Buntinx and Giuseppe Matullo and Rajiv Kumar and Mayordomo, \{Jos{\'e} I.\} and \{Gunnar Steineck\}, D. and Kiltie, \{Anne E.\} and Eirikur Jonsson and Fran{\c c}ois Radvanyi and Knowles, \{Margaret A.\} and Unnur Thorsteinsdottir and Kiemeney, \{Lambertus A.\} and Kari Stefansson",

note = "Publisher Copyright: {\textcopyright} The Author 2014.",

year = "2014",

month = nov,

day = "15",

doi = "10.1093/hmg/ddu264",

language = "English",

volume = "23",

pages = "5545--5557",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "20",

}

Rafnar, T, Sulem, P, Thorleifsson, G, Vermeulen, SH, Helgason, H, Saemundsdottir, J, Gudjonsson, SA, Sigurdsson, A, Stacey, SN, Gudmundsson, J, Johannsdottir, H, Alexiusdottir, K, Petursdottir, V, Nikulasson, S, Geirsson, G, Jonsson, T, Aben, KKH, Grotenhuis, AJ, Verhaegh, GW, Dudek, AM, Alfred Witjes, J, van der Heijden, AG, Vrieling, A, Galesloot, TE, De Juan, A, Panadero, A, Rivera, F, Hurst, C, Timothy Bishop, D, Sak, SC, Choudhury, A, Teo, MTW, Arici, C, Carta, A, Toninelli, E, de Verdier, P, Rudnai, P, Gurzau, E, Koppova, K, van der Keur, KA, Lurkin, I, Goossens, M, Kellen, E, Guarrera, S, Russo, A, Critelli, R, Sacerdote, C, Vineis, P, Krucker, C, Zeegers, MP, Gerullis, H, Ovsiannikov, D, Volkert, F, Hengstler, JG, Selinski, S, Magnusson, OT, Masson, G, Kong, A, Gudbjartsson, D, Lindblom, A, Zwarthoff, E, Porru, S, Golka, K, Buntinx, F, Matullo, G, Kumar, R, Mayordomo, JI, Gunnar Steineck, D, Kiltie, AE, Jonsson, E, Radvanyi, F, Knowles, MA, Thorsteinsdottir, U, Kiemeney, LA & Stefansson, K 2014, 'Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer', Human Molecular Genetics, vol. 23, no. 20, pp. 5545-5557. https://doi.org/10.1093/hmg/ddu264

TY - JOUR

T1 - Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer

AU - Rafnar, Thorunn

AU - Sulem, Patrick

AU - Thorleifsson, Gudmar

AU - Vermeulen, Sita H.

AU - Helgason, Hannes

AU - Saemundsdottir, Jona

AU - Gudjonsson, Sigurjon A.

AU - Sigurdsson, Asgeir

AU - Stacey, Simon N.

AU - Gudmundsson, Julius

AU - Johannsdottir, Hrefna

AU - Alexiusdottir, Kristin

AU - Petursdottir, Vigdis

AU - Nikulasson, Sigfus

AU - Geirsson, Gudmundur

AU - Jonsson, Thorvaldur

AU - Aben, Katja K.H.

AU - Grotenhuis, Anne J.

AU - Verhaegh, Gerald W.

AU - Dudek, Aleksandra M.

AU - Alfred Witjes, J.

AU - van der Heijden, Antoine G.

AU - Vrieling, Alina

AU - Galesloot, Tessel E.

AU - De Juan, Ana

AU - Panadero, Angeles

AU - Rivera, Fernando

AU - Hurst, Carolyn

AU - Timothy Bishop, D.

AU - Sak, Sei C.

AU - Choudhury, Ananya

AU - Teo, Mark T.W.

AU - Arici, Cecilia

AU - Carta, Angela

AU - Toninelli, Elena

AU - de Verdier, Petra

AU - Rudnai, Peter

AU - Gurzau, Eugene

AU - Koppova, Kvetoslava

AU - van der Keur, Kirstin A.

AU - Lurkin, Irene

AU - Goossens, Mieke

AU - Kellen, Eliane

AU - Guarrera, Simonetta

AU - Russo, Alessia

AU - Critelli, Rossana

AU - Sacerdote, Carlotta

AU - Vineis, Paolo

AU - Krucker, Clémentine

AU - Zeegers, Maurice P.

AU - Gerullis, Holger

AU - Ovsiannikov, Daniel

AU - Volkert, Frank

AU - Hengstler, Jan G.

AU - Selinski, Silvia

AU - Magnusson, Olafur T.

AU - Masson, Gisli

AU - Kong, Augustine

AU - Gudbjartsson, Daniel

AU - Lindblom, Annika

AU - Zwarthoff, Ellen

AU - Porru, Stefano

AU - Golka, Klaus

AU - Buntinx, Frank

AU - Matullo, Giuseppe

AU - Kumar, Rajiv

AU - Mayordomo, José I.

AU - Gunnar Steineck, D.

AU - Kiltie, Anne E.

AU - Jonsson, Eirikur

AU - Radvanyi, François

AU - Knowles, Margaret A.

AU - Thorsteinsdottir, Unnur

AU - Kiemeney, Lambertus A.

AU - Stefansson, Kari

PY - 2014/11/15

Y1 - 2014/11/15

N2 - Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC cases and 10 456 controls. We tested a dataset containing 34.2 million variants, generated by imputation based on whole-genome sequencing of 2230 Icelanders. Several correlated variants at 20p12, represented by rs62185668, show genome-wide significant association with UBC after combining discovery and replication results (OR = 1.19, P = 1.5 × 10-11 for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately kb upstream from the JAG1 gene, an important component of the Notch signaling pathways that may be oncogenic or tumor suppressive in several forms of cancer. Our results add to the growing number of UBC risk variants discovered through GWAS.

AB - Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC cases and 10 456 controls. We tested a dataset containing 34.2 million variants, generated by imputation based on whole-genome sequencing of 2230 Icelanders. Several correlated variants at 20p12, represented by rs62185668, show genome-wide significant association with UBC after combining discovery and replication results (OR = 1.19, P = 1.5 × 10-11 for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately kb upstream from the JAG1 gene, an important component of the Notch signaling pathways that may be oncogenic or tumor suppressive in several forms of cancer. Our results add to the growing number of UBC risk variants discovered through GWAS.

UR - https://www.scopus.com/pages/publications/84903486573

U2 - 10.1093/hmg/ddu264

DO - 10.1093/hmg/ddu264

M3 - Article

SN - 0964-6906

VL - 23

SP - 5545

EP - 5557

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 20

ER -

Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer

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