Title

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

Authors

David V. Conti
Burcu F. Darst
Lilit C. Moss
Edward J. Saunders
Xin Sheng
Alisha Chou
Fredrick R. Schumacher
Ali Amin Al Olama
Sara Benlloch
Tokhir Dadaev
Mark N. Brook
Ali Sahimi
Thomas J. Hoffmann
Atushi Takahashi
Koichi Matsuda
Yukihide Momozawa
Masashi Fujita
Kenneth Muir
Artitaya Lophatananon
Peggy Wan
Loic Le Marchand
Lynne R. Wilkens
Victoria L. Stevens
Susan M. Gapstur
Brian D. Carter
Johanna Schleutker
Teuvo LJ Tammela
Csilla Sipeky
Anssi Auvinen
Graham G. Giles
Melissa C. Southey
Robert J. MacInnis
Cezary Cybulski
Dominika Wokołorczyk
Jan Lubiński
David E. Neal
Jenny L. Donovan
Freddie C. Hamdy
Richard M. Martin
Børge G. Nordestgaard
Sune F. Nielsen
Maren Weischer
Stig E. Bojesen
Martin Andreas Røder
Peter Iversen
Jyotsna Batra
Suzanne Chambers
Leire Moya
Lisa Horvath
Judith A. Clements
Wayne Tilley
Gail P. Risbridger
Henrik Gronberg
Markus Aly
Robert Szulkin
Martin Eklund
Tobias Nordström
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 J. Weinstein
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
Milan S. Geybels
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 ML West
Neil Burnet
Gill Barnett
Christiane Maier
Thomas Schnoeller
Manuel Luedeke
Adam S. Kibel
Bettina F. Drake
Olivier Cussenot
Géraldine 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
Elizabeth TH Fontham
James Mohler
Jack A. Taylor
Manolis Kogevinas
Javier Llorca
Gemma Castaño-Vinyals
Lisa Cannon-Albright
Craig C. Teerlink
Chad D. Huff
Sara S. Strom
Luc Multigner
Pascal Blanchet
Laurent Brureau
Radka Kaneva
Chavdar Slavov
Vanio Mitev
Robin J. Leach
Brandi Weaver
Hermann Brenner
Katarina Cuk
Bernd Holleczek
Kai-Uwe Saum
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 JM 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 Neslund-Dudas
Benjamin A. Rybicki, Henry Ford Health SystemFollow
Marija Gamulin
Davor Lessel
Tomislav Kulis
Nawaid Usmani
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 C. Cullen
Gyorgy Petrovics
Graham Casey
Monique J. Roobol
Guido Jenster
Ron HN van Schaik
Jennifer J. Hu
Maureen Sanderson
Rohit Varma
Roberta McKean-Cowdin
Mina Torres
Nicholas Mancuso
Sonja I. Berndt
Stephen K. Van Den Eeden
Douglas F. Easton
Stephe J. Chanock
Michael B. Cook
Fredrik Wiklund
Hidewaki Nakagawa
John S. Witte
Rosalind A. Eeles
Zsofia Kote-Jarai
Christopher A. Haiman

Document Type

Article

Publication Date

1-1-2021

Publication Title

Nature genetics

Abstract

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

Medical Subject Headings

Continental Population Groups; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Middle Aged; Molecular Sequence Annotation; Neoplasm Invasiveness; Odds Ratio; Prostatic Neoplasms; Risk Factors

PubMed ID

33398198

Volume

53

Issue

1

First Page

65

Last Page

75

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