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. DudekJ. 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, P. 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 journalArticle

27 Citations (Scopus)

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 languageEnglish
Pages (from-to)5545-5557
Number of pages13
JournalHuman Molecular Genetics
Volume23
Issue number20
DOIs
Publication statusPublished - Nov 15 2014

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Genome-Wide Association Study
Urinary Bladder Neoplasms
Genome
Gene Components
Gene Frequency
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Rafnar, T., Sulem, P., Thorleifsson, G., Vermeulen, S. H., Helgason, H., Saemundsdottir, J., ... 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

Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer. / Rafnar, Thorunn; Sulem, Patrick; Thorleifsson, Gudmar; Vermeulen, Sita H.; Helgason, Hannes; Saemundsdottir, Jona; Gudjonsson, Sigurjon A.; Sigurdsson, Asgeir; Stacey, Simon N.; Gudmundsson, Julius; Johannsdottir, Hrefna; Alexiusdottir, Kristin; Petursdottir, Vigdis; Nikulasson, Sigfus; Geirsson, Gudmundur; Jonsson, Thorvaldur; Aben, Katja K H; Grotenhuis, Anne J.; Verhaegh, Gerald W.; Dudek, Aleksandra M.; Alfred Witjes, J.; van der Heijden, Antoine G.; Vrieling, Alina; Galesloot, Tessel E.; De Juan, Ana; Panadero, Angeles; Rivera, Fernando; Hurst, Carolyn; Timothy Bishop, D.; Sak, Sei C.; Choudhury, Ananya; Teo, Mark T W; Arici, Cecilia; Carta, Angela; Toninelli, Elena; de Verdier, Petra; Rudnai, P.; Gurzau, Eugene; Koppova, Kvetoslava; van der Keur, Kirstin A.; Lurkin, Irene; Goossens, Mieke; Kellen, Eliane; Guarrera, Simonetta; Russo, Alessia; Critelli, Rossana; Sacerdote, Carlotta; Vineis, Paolo; Krucker, Clémentine; Zeegers, Maurice P.; Gerullis, Holger; Ovsiannikov, Daniel; Volkert, Frank; Hengstler, Jan G.; Selinski, Silvia; Magnusson, Olafur T.; Masson, Gisli; Kong, Augustine; Gudbjartsson, Daniel; Lindblom, Annika; Zwarthoff, Ellen; Porru, Stefano; Golka, Klaus; Buntinx, Frank; Matullo, Giuseppe; Kumar, Rajiv; Mayordomo, José I.; Gunnar Steineck, D.; Kiltie, Anne E.; Jonsson, Eirikur; Radvanyi, François; Knowles, Margaret A.; Thorsteinsdottir, Unnur; Kiemeney, Lambertus A.; Stefansson, Kari.

In: Human Molecular Genetics, Vol. 23, No. 20, 15.11.2014, p. 5545-5557.

Research output: Contribution to journalArticle

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
Rafnar T, Sulem P, Thorleifsson G, Vermeulen SH, Helgason H, Saemundsdottir J et al. Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer. Human Molecular Genetics. 2014 Nov 15;23(20):5545-5557. https://doi.org/10.1093/hmg/ddu264
Rafnar, Thorunn ; Sulem, Patrick ; Thorleifsson, Gudmar ; Vermeulen, Sita H. ; Helgason, Hannes ; Saemundsdottir, Jona ; Gudjonsson, Sigurjon A. ; Sigurdsson, Asgeir ; Stacey, Simon N. ; Gudmundsson, Julius ; Johannsdottir, Hrefna ; Alexiusdottir, Kristin ; Petursdottir, Vigdis ; Nikulasson, Sigfus ; Geirsson, Gudmundur ; Jonsson, Thorvaldur ; Aben, Katja K H ; Grotenhuis, Anne J. ; Verhaegh, Gerald W. ; Dudek, Aleksandra M. ; Alfred Witjes, J. ; van der Heijden, Antoine G. ; Vrieling, Alina ; Galesloot, Tessel E. ; De Juan, Ana ; Panadero, Angeles ; Rivera, Fernando ; Hurst, Carolyn ; Timothy Bishop, D. ; Sak, Sei C. ; Choudhury, Ananya ; Teo, Mark T W ; Arici, Cecilia ; Carta, Angela ; Toninelli, Elena ; de Verdier, Petra ; Rudnai, P. ; Gurzau, Eugene ; Koppova, Kvetoslava ; van der Keur, Kirstin A. ; Lurkin, Irene ; Goossens, Mieke ; Kellen, Eliane ; Guarrera, Simonetta ; Russo, Alessia ; Critelli, Rossana ; Sacerdote, Carlotta ; Vineis, Paolo ; Krucker, Clémentine ; Zeegers, Maurice P. ; Gerullis, Holger ; Ovsiannikov, Daniel ; Volkert, Frank ; Hengstler, Jan G. ; Selinski, Silvia ; Magnusson, Olafur T. ; Masson, Gisli ; Kong, Augustine ; Gudbjartsson, Daniel ; Lindblom, Annika ; Zwarthoff, Ellen ; Porru, Stefano ; Golka, Klaus ; Buntinx, Frank ; Matullo, Giuseppe ; Kumar, Rajiv ; Mayordomo, José I. ; Gunnar Steineck, D. ; Kiltie, Anne E. ; Jonsson, Eirikur ; Radvanyi, François ; Knowles, Margaret A. ; Thorsteinsdottir, Unnur ; Kiemeney, Lambertus A. ; Stefansson, Kari. / Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer. In: Human Molecular Genetics. 2014 ; Vol. 23, No. 20. pp. 5545-5557.
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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.",
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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, P.

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.

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