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

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 Uchio; Michiaki Kubo; Yoichiro Kamatani; Artitaya Lophatananon; Peggy Wan; Caroline Andrews; Adriana Lori; Parichoy P. Choudhury; Johanna Schleutker; Teuvo L. J. Tammela; Csilla Sipeky; Anssi Auvinen; Graham G. Giles; Melissa C. Southey; Robert J. MacInnis; Cezary Cybulski; Dominika Wokolorczyk; Jan Lubinski; Christopher T. Rentsch; Kelly Cho; Benjamin H. Mcmahon; David E. Neal; Jenny L. Donovan; Freddie C. Hamdy; Richard M. Martin; Borge G. Nordestgaard; Sune F. Nielsen; Maren Weischer; Stig E. Bojesen; Andreas Røder; Hein V. Stroomberg; Jyotsna Batra; Suzanne Chambers; Lisa Horvath; Judith A. Clements; Wayne Tilly; Gail P. Risbridger; Henrik Gronberg; Markus Aly; Robert Szulkin; Martin Eklund; Tobias Nordstrom; Nora Pashayan; Alison M. Dunning; Maya Ghoussaini; Ruth C. Travis; Tim J. Key; Elio Riboli; Jong Y. Park; Thomas A. Sellers; Hui-Yi Lin; Demetrius Albanes; Stephanie Weinstein; Michael B. Cook; Lorelei A. Mucci; Edward Giovannucci; Sara Lindstrom; Peter Kraft; David J. Hunter; Kathryn L. Penney; Constance Turman; Catherine M. Tangen; Phyllis J. Goodman; Ian M. Thompson; Robert J. Hamilton; Neil E. Fleshner; Antonio Finelli; Marie-Élise Parent; Janet L. Stanford; Elaine A. Ostrander; Stella Koutros; Laura E. Beane Freeman; Meir Stampfer; Alicja Wolk; Niclas Håkansson; Gerald L. Andriole; Robert N. Hoover; Mitchell J. Machiela; Karina Dalsgaard Sørensen; Michael Borre; William J. Blot; Wei Zheng; Edward D. Yeboah; James E. Mensah; Yong-Jie Lu; Hong-Wei Zhang; Ninghan Feng; Xueying Mao; Yudong Wu; Shan-Chao Zhao; Zan Sun; Stephen N. Thibodeau; Shannon K. McDonnell; Daniel J. Schaid; Catharine M. L. West; Gill Barnett; Christiane Maier; Thomas Schnoeller; Manuel Luedeke; Adam S. Kibel; Bettina F. Drake; Olivier Cussenot; Geraldine Cancel-Tassin; Florence Menegaux; Thérèse Truong; Yves Akoli Koudou; Esther M. John; Eli Marie Grindedal; Lovise Maehle; Kay-Tee Khaw; Sue A. Ingles; Mariana C. Stern; Ana Vega; Antonio Gómez-Caamaño; Laura Fachal; Barry S. Rosenstein; Sarah L. Kerns; Harry Ostrer; Manuel R. Teixeira; Paula Paulo; Andreia Brandão; Stephen Watya; Alexander Lubwama; Jeannette T. Bensen; Ebonee N. Butler; James L. Mohler; Jack A. Taylor; Manolis Kogevinas; Trinidad Dierssen-Sotos; Gemma Castaño-Vinyals; Lisa Cannon-Albright; Craig C. Teerlink; Chad D. Huff; Patrick Pilie; Yao Yu; Ryan J. Bohlender; Jian Gu; Sara S. Strom; Luc Multigner; Pascal Blanchet; Laurent Brureau; Radka Kaneva; Chavdar Slavov; Vanio Mitev; Robin J. Leach; Hermann Brenner; Xuechen Chen; Bernd Holleczek; Ben Schöttker; Eric A. Klein; Ann W. Hsing; Rick A. Kittles; Adam B. Murphy; Christopher J. Logothetis; Jeri Kim; Susan L. Neuhausen; Linda Steele; Yuan Chun Ding; William B. Isaacs; Barbara Nemesure; Anselm J. M. Hennis; John Carpten; Hardev Pandha; Agnieszka Michael; Kim De Ruyck; Gert De Meerleer; Piet Ost; Jianfeng Xu; Azad Razack; Jasmine Lim; Soo-Hwang Teo; Lisa F. Newcomb; Daniel W. Lin; Jay H. Fowke; Christine M. Neslund-Dudas; Benjamin A. Rybicki; Marija Gamulin; Davor Lessel; Tomislav Kulis; Nawaid Usmani; Aswin Abraham; Sandeep Singhal; Matthew Parliament; Frank Claessens; Steven Joniau; Thomas Van den Broeck; Manuela Gago-Dominguez; Jose Esteban Castelao; Maria Elena Martinez; Samantha Larkin; Paul A. Townsend; Claire Aukim-Hastie; William S. Bush; Melinda C. Aldrich; Dana C. Crawford; Shiv Srivastava; Jennifer Cullen; Gyorgy Petrovics; Graham Casey; Ying Wang; Yao Tettey; Joseph Lachance; Wei Tang; Richard B. Biritwum; Andrew A. Adjei; Evelyn Tay; Ann Truelove; Shelley Niwa; Kosj Yamoah; Koveela Govindasami; Anand P. Chokkalingam; Jacob M. Keaton; Jacklyn N. Hellwege; Peter E. Clark; Mohamed Jalloh; Serigne M. Gueye; Lamine Niang; Olufemi Ogunbiyi; Olayiwola Shittu; Olukemi Amodu; Akindele O. Adebiyi; Oseremen I. Aisuodionoe-Shadrach; Hafees O. Ajibola; Mustapha A. Jamda; Olabode P. Oluwole; Maxwell Nwegbu; Ben Adusei; Sunny Mante; Afua Darkwa-Abrahams; Halimatou Diop; Susan M. Gundell; Monique J. Roobol; Guido Jenster; Ron H. N. van Schaik; Jennifer J. Hu; Maureen Sanderson; Linda Kachuri; Rohit Varma; Roberta McKean-Cowdin; Mina Torres; Michael H. Preuss; Ruth J. F. Loos; Matthew Zawistowski; Sebastian Zöllner; Zeyun Lu; Stephen K. Van Den Eeden; Douglas F. Easton; Stefan Ambs; Todd L. Edwards; Reedik Mägi; Timothy R. Rebbeck; Lars Fritsche; Stephen J. Chanock; Sonja I. Berndt; Fredrik Wiklund; Hidewaki Nakagawa; John S. Witte; J. Michael Gaziano; Amy C. Justice; Nick Mancuso; Chikashi Terao; Rosalind A. Eeles; Zsofia Kote-Jarai; Ravi K. Madduri; David V. Conti; The Biobank Japan Project; Christopher A. Haiman

doi:10.1038/s41588-023-01534-4

Back

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

Journal article

Peer reviewed

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

Anqi Wang, Jiayi Shen, Alex A. Rodriguez, Edward J. Saunders, Fei Chen, Rohini Janivara, Burcu F. Darst, Xin Sheng, Yili Xu, Alisha J. Chou, …

Nature genetics, Vol.55(12), pp.2065-2074

12/01/2023

DOI: https://doi.org/10.1038/s41588-023-01534-4

PMID: 37945903

Abstract and subjects

45/43

631/208/205/2138

692/308/2056

692/699/67/589/466

692/700/459/1748

Agriculture

Animal Genetics and Genomics

Biomedical and Life Sciences

Biomedicine

Cancer Research

Gene Function

General

Human Genetics

Letter

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. A multi-ancestry genome-wide association study of prostate cancer performed in 156,319 cases and 788,443 controls identifies 187 novel risk variants associated with the disease. Genetic risk scores associated with overall risk, and risk of aggressive disease in men of African ancestry.

Metrics

2 Record Views

See more details

Details

Title: Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
Authors/Creators - name: 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 Uchio
Michiaki Kubo
Yoichiro Kamatani
Artitaya Lophatananon
Peggy Wan
Caroline Andrews
Adriana Lori
Parichoy P. Choudhury
Johanna Schleutker
Teuvo L. J. Tammela
Csilla Sipeky
Anssi Auvinen
Graham G. Giles
Melissa C. Southey
Robert J. MacInnis
Cezary Cybulski
Dominika Wokolorczyk
Jan Lubinski
Christopher T. Rentsch
Kelly Cho
Benjamin H. Mcmahon
David E. Neal
Jenny L. Donovan
Freddie C. Hamdy
Richard M. Martin
Borge G. Nordestgaard
Sune F. Nielsen
Maren Weischer
Stig E. Bojesen
Andreas Røder
Hein V. Stroomberg
Jyotsna Batra
Suzanne Chambers
Lisa Horvath
Judith A. Clements
Wayne Tilly
Gail P. Risbridger
Henrik Gronberg
Markus Aly
Robert Szulkin
Martin Eklund
Tobias Nordstrom
Nora Pashayan
Alison M. Dunning
Maya Ghoussaini
Ruth C. Travis
Tim J. Key
Elio Riboli
Jong Y. Park
Thomas A. Sellers
Hui-Yi Lin
Demetrius Albanes
Stephanie Weinstein
Michael B. Cook
Lorelei A. Mucci
Edward Giovannucci
Sara Lindstrom
Peter Kraft
David J. Hunter
Kathryn L. Penney
Constance Turman
Catherine M. Tangen
Phyllis J. Goodman
Ian M. Thompson
Robert J. Hamilton
Neil E. Fleshner
Antonio Finelli
Marie-Élise Parent
Janet L. Stanford
Elaine A. Ostrander
Stella Koutros
Laura E. Beane Freeman
Meir Stampfer
Alicja Wolk
Niclas Håkansson
Gerald L. Andriole
Robert N. Hoover
Mitchell J. Machiela
Karina Dalsgaard Sørensen
Michael Borre
William J. Blot
Wei Zheng
Edward D. Yeboah
James E. Mensah
Yong-Jie Lu
Hong-Wei Zhang
Ninghan Feng
Xueying Mao
Yudong Wu
Shan-Chao Zhao
Zan Sun
Stephen N. Thibodeau
Shannon K. McDonnell
Daniel J. Schaid
Catharine M. L. West
Gill Barnett
Christiane Maier
Thomas Schnoeller
Manuel Luedeke
Adam S. Kibel
Bettina F. Drake
Olivier Cussenot
Geraldine Cancel-Tassin
Florence Menegaux
Thérèse Truong
Yves Akoli Koudou
Esther M. John
Eli Marie Grindedal
Lovise Maehle
Kay-Tee Khaw
Sue A. Ingles
Mariana C. Stern
Ana Vega
Antonio Gómez-Caamaño
Laura Fachal
Barry S. Rosenstein
Sarah L. Kerns
Harry Ostrer
Manuel R. Teixeira
Paula Paulo
Andreia Brandão
Stephen Watya
Alexander Lubwama
Jeannette T. Bensen
Ebonee N. Butler
James L. Mohler
Jack A. Taylor
Manolis Kogevinas
Trinidad Dierssen-Sotos
Gemma Castaño-Vinyals
Lisa Cannon-Albright
Craig C. Teerlink
Chad D. Huff
Patrick Pilie
Yao Yu
Ryan J. Bohlender
Jian Gu
Sara S. Strom
Luc Multigner
Pascal Blanchet
Laurent Brureau
Radka Kaneva
Chavdar Slavov
Vanio Mitev
Robin J. Leach
Hermann Brenner
Xuechen Chen
Bernd Holleczek
Ben Schöttker
Eric A. Klein
Ann W. Hsing
Rick A. Kittles
Adam B. Murphy
Christopher J. Logothetis
Jeri Kim
Susan L. Neuhausen
Linda Steele
Yuan Chun Ding
William B. Isaacs
Barbara Nemesure
Anselm J. M. Hennis
John Carpten
Hardev Pandha
Agnieszka Michael
Kim De Ruyck
Gert De Meerleer
Piet Ost
Jianfeng Xu
Azad Razack
Jasmine Lim
Soo-Hwang Teo
Lisa F. Newcomb
Daniel W. Lin
Jay H. Fowke
Christine M. Neslund-Dudas
Benjamin A. Rybicki
Marija Gamulin
Davor Lessel
Tomislav Kulis
Nawaid Usmani
Aswin Abraham
Sandeep Singhal
Matthew Parliament
Frank Claessens
Steven Joniau
Thomas Van den Broeck
Manuela Gago-Dominguez
Jose Esteban Castelao
Maria Elena Martinez
Samantha Larkin
Paul A. Townsend
Claire Aukim-Hastie
William S. Bush
Melinda C. Aldrich
Dana C. Crawford
Shiv Srivastava
Jennifer Cullen
Gyorgy Petrovics
Graham Casey
Ying Wang
Yao Tettey
Joseph Lachance
Wei Tang
Richard B. Biritwum
Andrew A. Adjei
Evelyn Tay
Ann Truelove
Shelley Niwa
Kosj Yamoah
Koveela Govindasami
Anand P. Chokkalingam
Jacob M. Keaton
Jacklyn N. Hellwege
Peter E. Clark
Mohamed Jalloh
Serigne M. Gueye
Lamine Niang
Olufemi Ogunbiyi
Olayiwola Shittu
Olukemi Amodu
Akindele O. Adebiyi
Oseremen I. Aisuodionoe-Shadrach
Hafees O. Ajibola
Mustapha A. Jamda
Olabode P. Oluwole
Maxwell Nwegbu
Ben Adusei
Sunny Mante
Afua Darkwa-Abrahams
Halimatou Diop
Susan M. Gundell
Monique J. Roobol
Guido Jenster
Ron H. N. van Schaik
Jennifer J. Hu
Maureen Sanderson
Linda Kachuri
Rohit Varma
Roberta McKean-Cowdin
Mina Torres
Michael H. Preuss
Ruth J. F. Loos
Matthew Zawistowski
Sebastian Zöllner
Zeyun Lu
Stephen K. Van Den Eeden
Douglas F. Easton
Stefan Ambs
Todd L. Edwards
Reedik Mägi
Timothy R. Rebbeck
Lars Fritsche
Stephen J. Chanock
Sonja I. Berndt
Fredrik Wiklund
Hidewaki Nakagawa
John S. Witte
J. Michael Gaziano
Amy C. Justice
Nick Mancuso
Chikashi Terao
Rosalind A. Eeles
Zsofia Kote-Jarai
Ravi K. Madduri
David V. Conti
The Biobank Japan Project
Christopher A. Haiman
Publication Details: Nature genetics, Vol.55(12), pp.2065-2074
Publisher: Nature Publishing Group US
Number of pages: 10
Language: English
Resource Type: Journal article
DOI: https://doi.org/10.1038/s41588-023-01534-4
Publication ISSN: 1061-4036; 1546-1718