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

The Biobank Japan Project

doi:10.1038/s41588-023-01534-4

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

The Biobank Japan Project

Department of Surgery

University of Southern California
Argonne National Laboratory
The Institute of Cancer Research
Georgia Institute of Technology
Fred Hutchinson Cancer Research Center
University of Cambridge
Karolinska Institutet
Harvard Medical School
University of California at San Francisco
University of California San Francisco
RIKEN
National Cerebral and Cardiovascular Center
University of Tokyo
University of Tartu
Faculty of Biology, Medicine and Health
Warwick Medical School
Shimane University
The University of Tokyo
The University of Tokyo
Iwate Medical University
Juntendo University Graduate School of Medicine
Nihon University School of Medicine
Tokushukai Group
Nippon Medical School
Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
Fukujuji Hospital
The Cancer Institute Hospital of the Japanese Foundation for Cancer Research
Shiga University of Medical Science
Osaka International Cancer Institute
Iizuka Hospital
National Hospital Organization Osaka National Hospital
Korle Bu Teaching Hospital
Dana-Farber Cancer Institute
American Cancer Society
University of Turku
University of Turku
Tampere University and Tampere University Hospital
Tampere University
Cancer Council Victoria
Centre for Epidemiology and Biostatistics
Monash University
Pomeranian Medical University in Szczecin
Yale University
London School of Hygiene & Tropical Medicine
VA Connecticut Healthcare System
VA Boston Healthcare System
NM 87545
University of Oxford
Cancer Research UK
Bristol Medical School
University Hospitals Bristol and Weston NHS Foundation Trust
University of Bristol
University of Copenhagen
Copenhagen University Hospital
Rigshospitalet
University of Copenhagen
Queensland University of Technology
Translational Research Institute Australia
University of Technology Sydney
Camperdown
Garvan Institute of Medical Research
University of Adelaide
Peter Maccallum Cancer Centre
Karolinska University Hospital
SDS Life Sciences
Karolinska Institutet
University College London
Wellcome Sanger Institute
Imperial College London
Moffitt Cancer Center
Louisiana State University Health Sciences Center
National Institutes of Health
Harvard T.H. Chan School of Public Health
University of Washington
Brigham and Women’s Hospital
CHRISTUS Santa Rosa Hospital
Princess Margaret Cancer Centre
University of Toronto
Centre Armand-Frappier Santé Biotechnologie
National Human Genome Research Institute (NHGRI)
Uppsala University
Johns Hopkins University
Aarhus University
Vanderbilt University
International Epidemiology Institute
University of Ghana
Queen Mary University of London
Second Military Medical University
Nanjing Medical University
First Affiliated Hospital of Zhengzhou University
Southern Medical University
China Medical University
Mayo Clinic Rochester, MN
Humangenetik Tuebingen
Ulm University Medical Center
Washington University St. Louis
Sorbonne Université
CeRePP
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Faculté de Médecine
Stanford Cancer Institute
University of Oslo
Fundación Pública Galega Medicina Xenómica
Instituto de Investigación Sanitaria de Santiago de Compostela
Centro de Investigación en Red de Enfermedades Raras
Complejo Hospitalario Universitario de Santiago
Icahn School of Medicine at Mount Sinai
Medical College of Wisconsin
Albert Einstein College of Medicine
Instituto Português de Oncologia do Porto Francisco Gentil E.P.E.
University of Porto
Uro Care
University of North Carolina
University of North Carolina at Chapel Hill
Roswell Park Cancer Institute
National Institute of Environmental Health Sciences (NIEHS)
Universitat de Barcelona
IMIM (Hospital del Mar Medical Research Institute)
Universitat Pompeu Fabra (UPF)
CIBER Epidemiología y Salud Pública (CIBERESP)
Universidad de Cantabria
University of Utah School of Medicine
VA Medical Center
The University of Texas MD Anderson Cancer Center
University Rennes
Paris Cité University and University of the Antilles
Medical University Sofia
University of Texas Health Science Center at San Antonio
German Cancer Research Center
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Cleveland Clinic Foundation
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University of Malaya
Sime Darby Berhad
University of Washington School of Medicine
University of Tennessee Health Science Center
Henry Ford Hospital
University of Zagreb
University Medical Center Hamburg-Eppendorf (UKE)
University of Alberta
Cross Cancer Institute
Molecular Endocrinology Laboratory
KU Leuven
Moores Cancer Center
Instituto de Investigación Biomédica Galicia Sur (IISGS)
University of California at San Diego
University of Southampton
School of Biosciences and Medicine
Scientific Education Support
Case Western Reserve University
Georgetown University
Uniformed Services University of the Health Sciences
University of Virginia School of Medicine
Westat
University of California, Berkeley
Atrium Health/Levine Cancer Institute
Hôpital Général Idrissa Pouye
College of Medicine, University of Ibadan
University of Abuja
37 Military Hospital
Hôpital Aristide Le Dantec
Erasmus University Rotterdam
Sylvester Comprehensive Cancer Center
Meharry Medical College
CHA Hollywood Presbyterian Medical Center
University of Michigan, Ann Arbor
Kaiser Permanente Division of Research
Stanford University
Shizuoka General Hospital
University of Shizuoka
Royal Marsden NHS Foundation Trust

Research output: Contribution to journal › Article › peer-review

99 Citations (Scopus)

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.

Original language	English
Pages (from-to)	2065-2074
Number of pages	10
Journal	Nature Genetics
Volume	55
Issue number	12
DOIs	https://doi.org/10.1038/s41588-023-01534-4
Publication status	Published - Dec 2023

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/s41588-023-01534-4

Cite this

@article{ff61d54184834aa198cede6dda41c458,

title = "Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants",

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.",

author = "\{The Biobank Japan Project\} and Anqi Wang and Jiayi Shen and Rodriguez, \{Alex A.\} and Saunders, \{Edward J.\} and Fei Chen and Rohini Janivara and Darst, \{Burcu F.\} and Xin Sheng and Yili Xu and Chou, \{Alisha J.\} and Sara Benlloch and Tokhir Dadaev and Brook, \{Mark N.\} and Anna Plym and Ali Sahimi and Hoffman, \{Thomas J.\} and Atushi Takahashi and Koichi Matsuda and Yukihide Momozawa and Masashi Fujita and Triin Laisk and J{\'e}ssica Figuer{\^e}do and Kenneth Muir and Shuji Ito and Xiaoxi Liu and Yuji Yamanashi and Yoichi Furukawa and Takayuki Morisaki and Yoshinori Murakami and Kaori Muto and Akiko Nagai and Wataru Obara and Ken Yamaji and Kazuhisa Takahashi and Satoshi Asai and Yasuo Takahashi and Takao Suzuki and Nobuaki Sinozaki and Hiroki Yamaguchi and Shiro Minami and Shigeo Murayama and Kozo Yoshimori and Satoshi Nagayama and Daisuke Obata and Masahiko Higashiyama and Akihide Masumoto and Yukihiro Koretsune and Yuji Uchio and Michiaki Kubo and Mensah, \{James E.\}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2023",

month = dec,

doi = "10.1038/s41588-023-01534-4",

language = "English",

volume = "55",

pages = "2065--2074",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "12",

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AU - The Biobank Japan Project

AU - Wang, Anqi

AU - Shen, Jiayi

AU - Rodriguez, Alex A.

AU - Saunders, Edward J.

AU - Chen, Fei

AU - Janivara, Rohini

AU - Darst, Burcu F.

AU - Sheng, Xin

AU - Xu, Yili

AU - Chou, Alisha J.

AU - Benlloch, Sara

AU - Dadaev, Tokhir

AU - Brook, Mark N.

AU - Plym, Anna

AU - Sahimi, Ali

AU - Hoffman, Thomas J.

AU - Takahashi, Atushi

AU - Matsuda, Koichi

AU - Momozawa, Yukihide

AU - Fujita, Masashi

AU - Laisk, Triin

AU - Figuerêdo, Jéssica

AU - Muir, Kenneth

AU - Ito, Shuji

AU - Liu, Xiaoxi

AU - Yamanashi, Yuji

AU - Furukawa, Yoichi

AU - Morisaki, Takayuki

AU - Murakami, Yoshinori

AU - Muto, Kaori

AU - Nagai, Akiko

AU - Obara, Wataru

AU - Yamaji, Ken

AU - Takahashi, Kazuhisa

AU - Asai, Satoshi

AU - Takahashi, Yasuo

AU - Suzuki, Takao

AU - Sinozaki, Nobuaki

AU - Yamaguchi, Hiroki

AU - Minami, Shiro

AU - Murayama, Shigeo

AU - Yoshimori, Kozo

AU - Nagayama, Satoshi

AU - Obata, Daisuke

AU - Higashiyama, Masahiko

AU - Masumoto, Akihide

AU - Koretsune, Yukihiro

AU - Uchio, Yuji

AU - Kubo, Michiaki

AU - Mensah, James E.

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85176259299

U2 - 10.1038/s41588-023-01534-4

DO - 10.1038/s41588-023-01534-4

M3 - Article

C2 - 37945903

AN - SCOPUS:85176259299

SN - 1061-4036

VL - 55

SP - 2065

EP - 2074

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

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

Abstract

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