Authors

Alexander Gusev
Huwenbo Shi
Gleb Kichaev
Mark Pomerantz
Fugen Li
Henry W. Long
Sue A. Ingles
Rick A. Kittles
Sara S. Strom
Benjamin A. Rybicki, Henry Ford Health SystemFollow
Barbara Nemesure
William G. Isaacs
Wei Zheng
Curtis A. Pettaway
Edward D. Yeboah
Yao Tettey
Richard B B. Biritwum
Andrew A. Adjei
Evelyn Tay
Ann Truelove
Shelley Niwa
Anand P. Chokkalingam
Esther M. John
Adam B. Murphy
Lisa B. Signorello
John Carpten
M C. Leske
Suh-Yuh Wu
Anslem JM Hennis
Christine Neslund-Dudas, Henry Ford Health SystemFollow
Ann W. Hsing
Lisa Chu
Phyllis J Goodman
Eric A Klein
John S Witte
Graham Casey
Sam Kaggwa
Michael B Cook
Daniel O Stram
William J Blot
Rosalind A Eeles
Douglas Easton
Zsofia Kote-Jarai
Ali Amin Al Olama
Sara Benlloch
Kenneth Muir
Graham G Giles
Melissa C Southey
Liesel M Fitzgerald
Henrik Gronberg
Fredrik Wiklund
Markus Aly
Brian E Henderson
Johanna Schleutker
Tiina Wahlfors
Teuvo L J Tammela
Børge G Nordestgaard
Tim J Key
Ruth C Travis
David E Neal
Jenny L Donovan
Freddie C Hamdy
Paul Pharoah
Nora Pashayan
Kay-Tee Khaw
Janet L Stanford
Stephen N Thibodeau
Shannon K McDonnell
Daniel J Schaid
Christiane Maier
Walther Vogel
Manuel Luedeke
Kathleen Herkommer
Adam S Kibel
Cezary Cybulski
Dominika Wokolorczyk
Wojciech Kluzniak
Lisa Cannon-Albright
Craig Teerlink
Hermann Brenner
Aida K Dieffenbach
Volker Arndt
Jong Y Park
Thomas A Sellers
Hui-Yi Lin
Chavdar Slavov
Radka Kaneva
Vanio Mitev
Jyotsna Batra
Amanda Spurdle
Judith A Clements
Manuel R Teixeira
Hardev Pandha
Agnieszka Michael
Paula Paulo
Sofia Maia
Andrzej Kierzek
David V Conti
Demetrius Albanes
Christine Berg
Sonja I Berndt
Daniele Campa
E David Crawford
W Ryan Diver
Susan M Gapstur
J Michael Gaziano
Edward Giovannucci
Robert Hoover
David J Hunter
Mattias Johansson
Peter Kraft
Loic Le Marchand
Sara Lindström
Carmen Navarro
Kim Overvad
Elio Riboli
Afshan Siddiq
Victoria L Stevens
Dimitrios Trichopoulos
Paolo Vineis
Meredith Yeager
Gosia Trynka
Soumya Raychaudhuri
Frederick R Schumacher
Alkes L Price
Matthew L Freedman
Christopher A Haiman
Bogdan Pasaniuc

Document Type

Article

Publication Date

4-7-2016

Publication Title

Nat Commun

Abstract

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.

Medical Subject Headings

Acetylation; African Americans; Atlases as Topic; Cell Line, Tumor; Epigenesis, Genetic; European Continental Ancestry Group; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Histones; Humans; Inheritance Patterns; Linkage Disequilibrium; Male; Polymorphism, Single Nucleotide; Prostatic Neoplasms

PubMed ID

27052111

Volume

7

First Page

10979

Last Page

10979

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