Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635–0.677) in African and 0.844 (95% CI = 0.840–0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67–2.00) and 2.19 (95% CI = 2.14–2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS269 had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659–0.700 and AUC = 0.845, 95% CI = 0.841–0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87–2.26 and OR = 2.21, 95% CI = 2.16–2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269 developed from multi-ancestry GWASs and fine-mapping.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | American Journal of Human Genetics |
| Vol/bind | 110 |
| Udgave nummer | 7 |
| Sider (fra-til) | 1200-1206 |
| Antal sider | 7 |
| ISSN | 0002-9297 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
This work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers U19 CA214253 to C.A.H. R01 CA257328 to C.A.H. U19 CA148537 to C.A.H. R01 CA165862 to C.A.H. and R00 CA246063 to B.F.D.), the Prostate Cancer Foundation (grants 21YOUN11 to B.F.D. and 20CHAS03 to C.A.H.), an award from the Andy Hill Cancer Research Endowment Distinguished Researchers Program (B.F.D.), a Fred Hutchinson Cancer Center/University of Washington SPORE Career Enhancement Program award (B.F.D.), and the Million Veteran Program-MVP017. This research has been conducted with the UK Biobank Resource under application number 42195. This research is based on data from the Million Veteran Program, Office of Research and Development, and the Veterans Health Administration. This publication does not represent the views of the Department of Veteran Affairs or the United States Government. Study conception/design: B.F.D. D.V.C. C.A.H.; provided data: R.K.M. X.S. E.J.S. T.D. M.N.B. T.J.H. K.M. P.W. L.L.M. L.W. Y.W. L.S. R.J.M. C.C. D.E.N. B.G.N. S.F.N. J.B. J.A.C. A.P.C.B. H.G. N.P. R.C.T. J.Y.P. D.A. S.W. L.A.M. D.J.H. K.L.P. C.M.T. R.J.H. M.P. J.L.S. S.K. A.W. K.D.S. W.J.B. E.D.Y. J.E.M. Y.L. S.N.T. C.M.W. C.M. A.S.K. G.C. F.M. E.M.J. E.M.G. K.K. S.A.I. A.V. B.S.B. M.R.T. N.C.P.I. M.K. L.C. C.H. L.M. R.K. R.J.L. H.B. A.W.H. R.A.K. A.B.M. C.J.L. S.L.N. W.B.I. B.N. A.J.H. J.C. H.P. K.D.R. J.X. A.R. S.T. C.P.I. L.F.N. J.F. C.N. B.A.R. M.G. N.U. F.C. M.G. J.E.C. P.A.T. D.C.C. G.P. G.C. M.F.R. J.F.H. S.I.B. S.K.V.D.E. D.F.E. S.J.C. M.B.C. F.W. J.S.W. R.A.E. A.K. S.W. J.M.G. A.C.J. D.V.C. C.A.H.; data analysis: B.F.D. J.S. Y.X. A.A.R.; bioinformatics support: X.S. R.K.M.; interpretation of data: B.F.D. D.V.C. C.A.H.; drafted the manuscript: B.F.D.; contributed to manuscript revisions: B.F.D. J.S. X.S. E.J.S. E.M.J. D.J.S. N.P. D.V.C. C.A.H.; all authors approved of the final manuscript. The authors have no conflicts of interest to disclose.
Funding Information:
This work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers U19 CA214253 to C.A.H., R01 CA257328 to C.A.H., U19 CA148537 to C.A.H., R01 CA165862 to C.A.H., and R00 CA246063 to B.F.D.), the Prostate Cancer Foundation (grants 21YOUN11 to B.F.D. and 20CHAS03 to C.A.H.), an award from the Andy Hill Cancer Research Endowment Distinguished Researchers Program (B.F.D.), a Fred Hutchinson Cancer Center/ University of Washington SPORE Career Enhancement Program award (B.F.D.), and the Million Veteran Program -MVP017. This research has been conducted with the UK Biobank Resource under application number 42195. This research is based on data from the Million Veteran Program, Office of Research and Development, and the Veterans Health Administration. This publication does not represent the views of the Department of Veteran Affairs or the United States Government.
Publisher Copyright:
© 2023 American Society of Human Genetics
Links
- https://www.medrxiv.org/content/10.1101/2023.05.12.23289860v1.full.pdf
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