Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

  • Anqi Wang
  • Jiayi Shen
  • Alex A. Rodriguez
  • Edward J. Saunders
  • Fei Chen
  • Rohini Janivara
  • Burcu F. Darst
  • Xin Sheng
  • Yili Xu
  • Alisha J. Chou
  • Sara Benlloch
  • Tokhir Dadaev
  • Mark N. Brook
  • Anna Plym
  • Ali Sahimi
  • Thomas J. Hoffman
  • Atushi Takahashi
  • Koichi Matsuda
  • Yukihide Momozawa
  • Masashi Fujita
  • Triin Laisk
  • Jéssica Figuerêdo
  • Kenneth Muir
  • Shuji Ito
  • Xiaoxi Liu
  • Yuji Yamanashi
  • Yoichi Furukawa
  • Takayuki Morisaki
  • Yoshinori Murakami
  • Kaori Muto
  • Akiko Nagai
  • Wataru Obara
  • Ken Yamaji
  • Kazuhisa Takahashi
  • Satoshi Asai
  • Yasuo Takahashi
  • Takao Suzuki
  • Nobuaki Sinozaki
  • Hiroki Yamaguchi
  • Nordestgaard, Børge
  • Sune F. Nielsen
  • Maren Weischer
  • Bojesen, Stig Egil
  • Røder, Andreas
  • Stroomberg, Hein Vincent
  • Karina Dalsgaard Sørensen
  • Michael Borre
  • Sara S. Strom
  • Ying Wang
  • Ruth J.F. Loos
  • The Biobank Japan Project
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.
OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind55
Udgave nummer12
Sider (fra-til)2065-2074
Antal sider10
ISSN1061-4036
DOI
StatusUdgivet - 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.

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