Abstract
The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Nature Genetics |
| Vol/bind | 55 |
| Udgave nummer | 12 |
| Sider (fra-til) | 2065-2074 |
| Antal sider | 10 |
| ISSN | 1061-4036 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:This project was supported by the US National Institutes of Health (NIH) grants R01CA257328 (C.A.H.), U19CA214253 (C.A.H.), U01CA261339 (D.V.C.), P01CA196569 (D.V.C.) and R00CA246063 (B.F. Darst), and the Prostate Cancer Foundation grants 20CHAS03 (CAH) and 21YOUN11 (B.F. Darst). We acknowledge support from The National Institute of Health Research to The Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, the DJ Fielding Medical Trust and the Joseph Fraser Trust via The Royal Marsden Cancer Charity. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. This research has been conducted using 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 US Government. A full description of funding and acknowledgements for each of the contributing studies can be found in the Supplementary Note.
Funding Information:
This project was supported by the US National Institutes of Health (NIH) grants R01CA257328 (C.A.H.), U19CA214253 (C.A.H.), U01CA261339 (D.V.C.), P01CA196569 (D.V.C.) and R00CA246063 (B.F. Darst), and the Prostate Cancer Foundation grants 20CHAS03 (CAH) and 21YOUN11 (B.F. Darst). We acknowledge support from The National Institute of Health Research to The Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, the DJ Fielding Medical Trust and the Joseph Fraser Trust via The Royal Marsden Cancer Charity. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. This research has been conducted using 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 US Government. A full description of funding and acknowledgements for each of the contributing studies can be found in the Supplementary Note.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.