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

T. Rafnar; P. Sulem; G. Thorleifsson; S.H. Vermeulen; H. Helgason; J. Saemundsdottir; S.A. Gudjonsson; A. Sigurdsson; S.N. Stacey; J. Gudmundsson; H. Johannsdottir; K. Alexiusdottir; V. Petursdottir; S. Nikulasson; G. Geirsson; T. Jonsson; K.K.H. Aben; A.J. Grotenhuis; G.W. Verhaegh; A.M. Dudek; J.A. Witjes; A.G. van der Heijden; A. Vrieling; T.E. Galesloot; A. De Juan; A. Panadero; F. Rivera; C. Hurst; D.T. Bishop; S.C. Sak; A. Choudhury; M.T.W. Teo; C. Arici; A. Carta; E. Toninelli; P. de Verdier; P. Rudnai; E. Gurzau; K. Koppova; K.A. van der Keur; I. Lurkin; M. Goossens; E. Kellen; S. Guarrera; A. Russo; R. Critelli; C. Sacerdote; P. Vineis; C. Krucker; M.P. Zeegers; H. Gerullis; D. Ovsiannikov; F. Volkert; J.G. Hengstler; S. Selinski; O.T. Magnusson; G. Masson; A. Kong; D. Gudbjartsson; A. Lindblom; E. Zwarthoff; S. Porru; K. Golka; F. Buntinx; G. Matullo; R. Kumar; J.I. Mayordomo; D.G. Steineck; A.E. Kiltie; E. Jonsson; F. Radvanyi; M.A. Knowles; U. Thorsteinsdottir; L.A. Kiemeney; K. Stefansson

doi:10.1093/hmg/ddu264

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

T. Rafnar^*, P. Sulem, G. Thorleifsson, S.H. Vermeulen, H. Helgason, J. Saemundsdottir, S.A. Gudjonsson, A. Sigurdsson, S.N. Stacey, J. Gudmundsson, H. Johannsdottir, K. Alexiusdottir, V. Petursdottir, S. Nikulasson, G. Geirsson, T. Jonsson, K.K.H. Aben, A.J. Grotenhuis, G.W. Verhaegh, A.M. DudekJ.A. Witjes, A.G. van der Heijden, A. Vrieling, T.E. Galesloot, A. De Juan, A. Panadero, F. Rivera, C. Hurst, D.T. Bishop, S.C. Sak, A. Choudhury, M.T.W. Teo, C. Arici, A. Carta, E. Toninelli, P. de Verdier, P. Rudnai, E. Gurzau, K. Koppova, K.A. van der Keur, I. Lurkin, M. Goossens, E. Kellen, S. Guarrera, A. Russo, R. Critelli, C. Sacerdote, P. Vineis, C. Krucker, M.P. Zeegers, H. Gerullis, D. Ovsiannikov, F. Volkert, J.G. Hengstler, S. Selinski, O.T. Magnusson, G. Masson, A. Kong, D. Gudbjartsson, A. Lindblom, E. Zwarthoff, S. Porru, K. Golka, F. Buntinx, G. Matullo, R. Kumar, J.I. Mayordomo, D.G. Steineck, A.E. Kiltie, E. Jonsson, F. Radvanyi, M.A. Knowles, U. Thorsteinsdottir, L.A. Kiemeney, K. Stefansson

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › 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 x 10-11 for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately 300 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 Oct 2014

Keywords

DNA-REPAIR GENES
UROTHELIAL CELL-CARCINOMA
CONFERS SUSCEPTIBILITY
SEQUENCE VARIANT
RISK
POLYMORPHISMS
EXPRESSION
METAANALYSIS
IMPUTATION
DISEASES

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10.1093/hmg/ddu264

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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{b754279767644107906870cbc9ecad14,

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 x 10-11 for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately 300 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.",

keywords = "DNA-REPAIR GENES, UROTHELIAL CELL-CARCINOMA, CONFERS SUSCEPTIBILITY, SEQUENCE VARIANT, RISK, POLYMORPHISMS, EXPRESSION, METAANALYSIS, IMPUTATION, DISEASES",

author = "T. Rafnar and P. Sulem and G. Thorleifsson and S.H. Vermeulen and H. Helgason and J. Saemundsdottir and S.A. Gudjonsson and A. Sigurdsson and S.N. Stacey and J. Gudmundsson and H. Johannsdottir and K. Alexiusdottir and V. Petursdottir and S. Nikulasson and G. Geirsson and T. Jonsson and K.K.H. Aben and A.J. Grotenhuis and G.W. Verhaegh and A.M. Dudek and J.A. Witjes and {van der Heijden}, A.G. and A. Vrieling and T.E. Galesloot and {De Juan}, A. and A. Panadero and F. Rivera and C. Hurst and D.T. Bishop and S.C. Sak and A. Choudhury and M.T.W. Teo and C. Arici and A. Carta and E. Toninelli and {de Verdier}, P. and P. Rudnai and E. Gurzau and K. Koppova and {van der Keur}, K.A. and I. Lurkin and M. Goossens and E. Kellen and S. Guarrera and A. Russo and R. Critelli and C. Sacerdote and P. Vineis and C. Krucker and M.P. Zeegers and H. Gerullis and D. Ovsiannikov and F. Volkert and J.G. Hengstler and S. Selinski and O.T. Magnusson and G. Masson and A. Kong and D. Gudbjartsson and A. Lindblom and E. Zwarthoff and S. Porru and K. Golka and F. Buntinx and G. Matullo and R. Kumar and J.I. Mayordomo and D.G. Steineck and A.E. Kiltie and E. Jonsson and F. Radvanyi and M.A. Knowles and U. Thorsteinsdottir and L.A. Kiemeney and K. Stefansson",

year = "2014",

month = oct,

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, Witjes, JA, van der Heijden, AG, Vrieling, A, Galesloot, TE, De Juan, A, Panadero, A, Rivera, F, Hurst, C, Bishop, DT, 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, Steineck, DG, 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, T.

AU - Sulem, P.

AU - Thorleifsson, G.

AU - Vermeulen, S.H.

AU - Helgason, H.

AU - Saemundsdottir, J.

AU - Gudjonsson, S.A.

AU - Sigurdsson, A.

AU - Stacey, S.N.

AU - Gudmundsson, J.

AU - Johannsdottir, H.

AU - Alexiusdottir, K.

AU - Petursdottir, V.

AU - Nikulasson, S.

AU - Geirsson, G.

AU - Jonsson, T.

AU - Aben, K.K.H.

AU - Grotenhuis, A.J.

AU - Verhaegh, G.W.

AU - Dudek, A.M.

AU - Witjes, J.A.

AU - van der Heijden, A.G.

AU - Vrieling, A.

AU - Galesloot, T.E.

AU - De Juan, A.

AU - Panadero, A.

AU - Rivera, F.

AU - Hurst, C.

AU - Bishop, D.T.

AU - Sak, S.C.

AU - Choudhury, A.

AU - Teo, M.T.W.

AU - Arici, C.

AU - Carta, A.

AU - Toninelli, E.

AU - de Verdier, P.

AU - Rudnai, P.

AU - Gurzau, E.

AU - Koppova, K.

AU - van der Keur, K.A.

AU - Lurkin, I.

AU - Goossens, M.

AU - Kellen, E.

AU - Guarrera, S.

AU - Russo, A.

AU - Critelli, R.

AU - Sacerdote, C.

AU - Vineis, P.

AU - Krucker, C.

AU - Zeegers, M.P.

AU - Gerullis, H.

AU - Ovsiannikov, D.

AU - Volkert, F.

AU - Hengstler, J.G.

AU - Selinski, S.

AU - Magnusson, O.T.

AU - Masson, G.

AU - Kong, A.

AU - Gudbjartsson, D.

AU - Lindblom, A.

AU - Zwarthoff, E.

AU - Porru, S.

AU - Golka, K.

AU - Buntinx, F.

AU - Matullo, G.

AU - Kumar, R.

AU - Mayordomo, J.I.

AU - Steineck, D.G.

AU - Kiltie, A.E.

AU - Jonsson, E.

AU - Radvanyi, F.

AU - Knowles, M.A.

AU - Thorsteinsdottir, U.

AU - Kiemeney, L.A.

AU - Stefansson, K.

PY - 2014/10/15

Y1 - 2014/10/15

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 x 10-11 for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately 300 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 x 10-11 for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately 300 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.

KW - DNA-REPAIR GENES

KW - UROTHELIAL CELL-CARCINOMA

KW - CONFERS SUSCEPTIBILITY

KW - SEQUENCE VARIANT

KW - RISK

KW - POLYMORPHISMS

KW - EXPRESSION

KW - METAANALYSIS

KW - IMPUTATION

KW - DISEASES

U2 - 10.1093/hmg/ddu264

DO - 10.1093/hmg/ddu264

M3 - Article

C2 - 24861552

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

Abstract

Keywords

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