Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

Fredrick R. Schumacher; Ali Amin Al Olama; Sonja I. Berndt; Sara Benlloch; Mahbubl Ahmed; Edward J. Saunders; Tokhir Dadaev; Daniel Leongamornlert; Ezequiel Anokian; Clara Cieza-Borrella; Chee Goh; Mark N. Brook; Xin Sheng; Laura Fachal; Joe Dennis; Jonathan Tyrer; Kenneth Muir; Artitaya Lophatananon; Victoria L. Stevens; Susan M. Gapstur; Brian D. Carter; Catherine M. Tangen; Phyllis J. Goodman; Ian M. Thompson; Jyotsna Batra; Suzanne Chambers; Leire Moya; Judith Clements; Lisa Horvath; Wayne Tilley; Gail P. Risbridger; Henrik Gronberg; Markus Aly; Tobias Nordström; Paul Pharoah; Nora Pashayan; Johanna Schleutker; Teuvo L. J. Tammela; Csilla Sipeky; Anssi Auvinen; Demetrius Albanes; Stephanie Weinstein; Alicja Wolk; Niclas Håkansson; Catharine M. L. West; Alison M. Dunning; Neil Burnet; Lorelei A. Mucci; Edward Giovannucci; Gerald L. Andriole; Olivier Cussenot; Géraldine Cancel-Tassin; Stella Koutros; Laura E. Beane Freeman; Karina Dalsgaard Sorensen; Torben Falck Orntoft; Michael Borre; Lovise Maehle; Eli Marie Grindedal; David E. Neal; Jenny L. Donovan; Freddie C. Hamdy; Richard M. Martin; Ruth C. Travis; Tim J. Key; Robert J. Hamilton; Neil E. Fleshner; Antonio Finelli; Sue Ann Ingles; Mariana C. Stern; Barry S. Rosenstein; Sarah L. Kerns; Harry Ostrer; Yong-Jie Lu; Hong-Wei Zhang; Ninghan Feng; Xueying Mao; Xin Guo; Guomin Wang; Zan Sun; Graham G. Giles; Melissa C. Southey; Robert J. MacInnis; Liesel M. FitzGerald; Adam S. Kibel; Bettina F. Drake; Ana Vega; Antonio Gómez-Caamaño; Robert Szulkin; Martin Eklund; Manolis Kogevinas; Javier Llorca; Gemma Castaño-Vinyals; Kathryn L. Penney; Meir Stampfer; Jong Y. Park; Thomas A. Sellers; Hui-Yi Lin; Janet L. Stanford; Cezary Cybulski; Dominika Wokolorczyk; Jan Lubinski; Elaine A. Ostrander; Milan S. Geybels; Børge G. Nordestgaard; Sune F. Nielsen; Maren Weischer; Rasmus Bisbjerg; Martin Andreas Røder; Peter Iversen; Hermann Brenner; Katarina Cuk; Bernd Holleczek; Christiane Maier; Manuel Luedeke; Thomas Schnoeller; Jeri Kim; Christopher J. Logothetis; Esther M. John; Manuel R. Teixeira; Paula Paulo; Marta Cardoso; Susan L. Neuhausen; Linda Steele; Yuan Chun Ding; Kim De Ruyck; Gert De Meerleer; Piet Ost; Azad Razack; Jasmine Lim; Soo-Hwang Teo; Daniel W. Lin; Lisa F. Newcomb; Davor Lessel; Marija Gamulin; Tomislav Kulis; Radka Kaneva; Nawaid Usmani; Sandeep Singhal; Chavdar Slavov; Vanio Mitev; Matthew Parliament; Frank Claessens; Steven Joniau; Thomas Van den Broeck; Samantha Larkin; Paul A. Townsend; Claire Aukim-Hastie; Manuela Gago Dominguez; Jose Esteban Castelao; Maria Elena Martinez; Monique J. Roobol; Guido Jenster; Ron H. N. van Schaik; Florence Menegaux; Thérèse Truong; Yves Akoli Koudou; Jianfeng Xu; Kay-Tee Khaw; Lisa Cannon-Albright; Hardev Pandha; Agnieszka Michael; Stephen N. Thibodeau; Shannon K. McDonnell; Daniel J. Schaid; Sara Lindstrom; Constance Turman; Jing Ma; David J. Hunter; Elio Riboli; Afshan Siddiq; Federico Canzian; Laurence N. Kolonel; Loic Le Marchand; Robert N. Hoover; Mitchell J. Machiela; Zuxi Cui; Peter Kraft; Christopher I. Amos; David V. Conti; Douglas F. Easton; Fredrik Wiklund; Stephen J. Chanock; Brian E. Henderson; Zsofia Kote-Jarai; Christopher A. Haiman; Rosalind A. Eeles

doi:10.1038/s41588-018-0142-8

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Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

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Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

Fredrick R. Schumacher, Ali Amin Al Olama, Sonja I. Berndt, Sara Benlloch, Mahbubl Ahmed, Edward J. Saunders, Tokhir Dadaev, Daniel Leongamornlert, Ezequiel Anokian, Clara Cieza-Borrella, …

Nature Genetics, Vol.50(7), pp.928-936

11/06/2018

DOI: https://doi.org/10.1038/s41588-018-0142-8

Abstract

Epidemiology; Genetic association study; Prostate cancer

Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P ˂ 5.0 × 10⁻⁸) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10⁻⁹; G˃C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10⁻⁹; T˃G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55–2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04–6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa.

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Title: Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci
Creators: Fredrick R. Schumacher
Ali Amin Al Olama
Sonja I. Berndt
Sara Benlloch
Mahbubl Ahmed
Edward J. Saunders
Tokhir Dadaev
Daniel Leongamornlert
Ezequiel Anokian
Clara Cieza-Borrella
Chee Goh
Mark N. Brook
Xin Sheng
Laura Fachal
Joe Dennis
Jonathan Tyrer
Kenneth Muir
Artitaya Lophatananon
Victoria L. Stevens
Susan M. Gapstur
Brian D. Carter
Catherine M. Tangen
Phyllis J. Goodman
Ian M. Thompson
Jyotsna Batra
Suzanne Chambers
Leire Moya
Judith Clements
Lisa Horvath
Wayne Tilley
Gail P. Risbridger
Henrik Gronberg
Markus Aly
Tobias Nordström
Paul Pharoah
Nora Pashayan
Johanna Schleutker
Teuvo L. J. Tammela
Csilla Sipeky
Anssi Auvinen
Demetrius Albanes
Stephanie Weinstein
Alicja Wolk
Niclas Håkansson
Catharine M. L. West
Alison M. Dunning
Neil Burnet
Lorelei A. Mucci
Edward Giovannucci
Gerald L. Andriole
Olivier Cussenot
Géraldine Cancel-Tassin
Stella Koutros
Laura E. Beane Freeman
Karina Dalsgaard Sorensen
Torben Falck Orntoft
Michael Borre
Lovise Maehle
Eli Marie Grindedal
David E. Neal
Jenny L. Donovan
Freddie C. Hamdy
Richard M. Martin
Ruth C. Travis
Tim J. Key
Robert J. Hamilton
Neil E. Fleshner
Antonio Finelli
Sue Ann Ingles
Mariana C. Stern
Barry S. Rosenstein
Sarah L. Kerns
Harry Ostrer
Yong-Jie Lu
Hong-Wei Zhang
Ninghan Feng
Xueying Mao
Xin Guo
Guomin Wang
Zan Sun
Graham G. Giles
Melissa C. Southey
Robert J. MacInnis
Liesel M. FitzGerald
Adam S. Kibel
Bettina F. Drake
Ana Vega
Antonio Gómez-Caamaño
Robert Szulkin
Martin Eklund
Manolis Kogevinas
Javier Llorca
Gemma Castaño-Vinyals
Kathryn L. Penney
Meir Stampfer
Jong Y. Park
Thomas A. Sellers
Hui-Yi Lin
Janet L. Stanford
Cezary Cybulski
Dominika Wokolorczyk
Jan Lubinski
Elaine A. Ostrander
Milan S. Geybels
Børge G. Nordestgaard
Sune F. Nielsen
Maren Weischer
Rasmus Bisbjerg
Martin Andreas Røder
Peter Iversen
Hermann Brenner
Katarina Cuk
Bernd Holleczek
Christiane Maier
Manuel Luedeke
Thomas Schnoeller
Jeri Kim
Christopher J. Logothetis
Esther M. John
Manuel R. Teixeira
Paula Paulo
Marta Cardoso
Susan L. Neuhausen
Linda Steele
Yuan Chun Ding
Kim De Ruyck
Gert De Meerleer
Piet Ost
Azad Razack
Jasmine Lim
Soo-Hwang Teo
Daniel W. Lin
Lisa F. Newcomb
Davor Lessel
Marija Gamulin
Tomislav Kulis
Radka Kaneva
Nawaid Usmani
Sandeep Singhal
Chavdar Slavov
Vanio Mitev
Matthew Parliament
Frank Claessens
Steven Joniau
Thomas Van den Broeck
Samantha Larkin
Paul A. Townsend
Claire Aukim-Hastie
Manuela Gago Dominguez
Jose Esteban Castelao
Maria Elena Martinez
Monique J. Roobol
Guido Jenster
Ron H. N. van Schaik
Florence Menegaux
Thérèse Truong
Yves Akoli Koudou
Jianfeng Xu
Kay-Tee Khaw
Lisa Cannon-Albright
Hardev Pandha
Agnieszka Michael
Stephen N. Thibodeau
Shannon K. McDonnell
Daniel J. Schaid
Sara Lindstrom
Constance Turman
Jing Ma
David J. Hunter
Elio Riboli
Afshan Siddiq
Federico Canzian
Laurence N. Kolonel
Loic Le Marchand
Robert N. Hoover
Mitchell J. Machiela
Zuxi Cui
Peter Kraft
Christopher I. Amos
David V. Conti
Douglas F. Easton
Fredrik Wiklund
Stephen J. Chanock
Brian E. Henderson
Zsofia Kote-Jarai
Christopher A. Haiman
Rosalind A. Eeles
Publication Details: Nature Genetics, Vol.50(7), pp.928-936
Publisher: Nature Publishing Group
Date published: 11/06/2018
Date submitted: 09/07/2018
Identifiers: 99513328902346
Academic Unit: School of Biosciences; Faculty of Health and Medical Sciences
Resource Type: Journal article

Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

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