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A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

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Abstract

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of >10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10−8; 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease.

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Figure 1: Manhattan plot of genotyped and imputed results from the European-ancestry meta-analysis of overall prostate cancer risk.
Figure 2: Manhattan plot of the results from the multi-ancestry meta-analysis of overall prostate cancer risk.
Figure 3: Regional plots of two new genome-wide significant loci associated with prostate cancer risk.

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Acknowledgements

A full list of acknowledgments is detailed in the Supplementary Note.

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Authors and Affiliations

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Contributions

A.H., R.A.E., Z.K.-J., D.F.E., B.E.H., S.J.C., S.I.B., P. Kraft, F.W., H.N. and M.B.C. designed the study. C.A.H., Z.K.-J., A.A.A.O. and R.A.E. wrote the manuscript. A.A.A.O., F.S., Y.H., Z.W., P.W., C. Chen, E.S., D.L., K.R., T.D., S.J.-L. and K.L.P. performed the statistical analysis. D.O.S. and D.V.C. provided statistical support. D.J. Hazelett, A. Stram, K.P., X.S., G.A.C., Q.L. and M.L.F. provided bioinformatics support as well as functional annotation and QTL data. L.C.P., K.P., L.X., L.B. and M.T. conducted the genotyping and sequencing. S.B., C.G. and M. Ahmed managed the PRACTICAL and COGS database. K.G. and M.G. managed the UKGPCS database. The following authors provided samples and/or data to the study and commented on the manuscript: J.T., T.V., K.A.L., K.-T.K., S.K.M., D.J.S., S.H., B.K., A.H.C., A.P.C., D.W., W.K., A.W.P. and E.M.G. L.N.K., L.L.M. and B.E.H. are principal investigators of the MEC. J.X. and S.L.Z. are principal investigators of NCPCS. R.C.T., T.J.K., A. Siddiq and F.C. are EPIC investigators. E.R. is the principal investigator of EPIC. A. Takahashi, M.K. and H.N. are principal investigators of BBJ. J.L.S. is the principal investigator of KCPCS; S.K. coordinated data collection. V.L.S. and W.R.D. are investigators and S.M.G. is the principal investigator of CPSII. S.S.S. and C.P. are principal investigators of the MDA prostate cancer studies. S.L., D.J. Hunter, P. Kraft, L.M., E.L.G., J.M. and M. Stampfer are coinvestigators of the Harvard cohorts and BPC3. H.G. is principal investigator of CAPS and STHLM1. M. Aly and F.W. are investigators of CAPS. W.B.I. is the principal investigator of the IPCG study. A.S.K. is the principal investigator of WUGS. E.M.J. is the principal investigator of SFPCS. S.A.I. is the principal investigator of LAAPC. R.A.K. and A.B.M. are investigators of DCPC. W.B., L.B.S. and W.Z. are principal investigators of SCCS. D.A. and J.V. are principal investigators and S.W. is the study coordinator of ATBC. B.N., J. Carpten, C.L., S.-Y.W. and A. Hennis are principal investigators of PCBP. B.A.R. and C.N.-D. are principal investigators of GECAP. J.S.W. and G.C. are principal investigators of CaP Genes. D.S. is the program officer of GAME-ON. P.J.G., E.A.K., A.W.H. and L.C. are investigators of SELECT. F.C.H., J.D. and D.E.N. are principal investigators of ProtecT. E.D.Y., Y.T., R.B.B., A.A.A., E.T., A. Truelove, S.N. and A.W.H. are investigators of the Ghana Prostate Study. S.J.C., S.I.B., R.N.H., M.J.M., M.Y., C.C.C., A. Hutchinson and K.Y. are investigators of PLCO. M.R.T. is the principal investigator and P. Paulo and S.M. are investigators of IPO-Porto. J.B., J. Clements and A. Spurdle are principal investigators of QLD. R.K. and C. Slavov are the principal investigators and V.M. is an investigator of PCMUS. J.P., T.S. and H.-Y.L. are the investigators of the MOFFITT study. L.C.-A. is the principal investigator of the Utah study. C. Cybulski is the principal investigator of the Poland study. S.N.T. is the principal investigator of the Mayo study. P. Pharoah and N.P. are investigators of SEARCH. C.M. is the principal investigator of ULM; M.L., K.H. and A.E.R. are investigators of ULM. M.W., S.F.N., B.G.N., P. Klarskov, M.A.R. and P.I. are the principal investigators of CPCS1 and CPCS2. T.W., A.A. and T.L.J.T. are investigators and J.S. is the principal investigator of TAMPERE. K.M. is a UKGPCS investigator. H.B. is the principal investigator, A.K.D. prepared the data and C. Stegmaier coordinated the data collection of the ESTHER study. G.G.G. and G.S. are the principal investigators of MCCS; M. Southey is an investigator and H.P., A.M. and A.M.K. are principal investigators of the PPF-UNIS study.

Corresponding authors

Correspondence to Rosalind A Eeles or Christopher A Haiman.

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The authors declare no competing financial interests.

Additional information

A complete list of all consortia members is provided in the Supplementary Note.

A complete list of all consortia members is provided in the Supplementary Note.

A complete list of all consortia members is provided in the Supplementary Note.

A complete list of all consortia members is provided in the Supplementary Note.

Supplementary information

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Al Olama, A., Kote-Jarai, Z., Berndt, S. et al. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nat Genet 46, 1103–1109 (2014). https://doi.org/10.1038/ng.3094

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