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 journalArticleAcademicpeer-review


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


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