Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.

Nat Commun
Authors
Alexander Gusev
Huwenbo Shi
Gleb Kichaev
Mark Pomerantz
Fugen Li
Henry Long
Sue Ingles
Rick Kittles
Sara Strom
Benjamin Rybicki
Barbara Nemesure
William Isaacs
Wei Zheng
Curtis Pettaway
Edward Yeboah
Yao Tettey
Richard Biritwum
Andrew Adjei
Evelyn Tay
Ann Truelove
Shelley Niwa
Anand Chokkalingam
Esther John
Adam Murphy
Lisa Signorello
John Carpten
M Cristina Leske
Suh-Yuh Wu
Anslem Hennis
Christine Neslund-Dudas
Ann Hsing
Lisa Chu
Phyllis Goodman
Eric Klein
John Witte
Graham Casey
Sam Kaggwa
Michael Cook
Daniel Stram
William Blot
Rosalind Eeles
Douglas Easton
Zsofia Kote-Jarai
Ali Olama
Sara Benlloch
Kenneth Muir
Graham Giles
Melissa Southey
Liesel Fitzgerald
Henrik Gronberg
Fredrik Wiklund
Markus Aly
Brian Henderson
Johanna Schleutker
Tiina Wahlfors
Teuvo Tammela
Børge Nordestgaard
Tim Key
Ruth Travis
David Neal
Jenny Donovan
Freddie Hamdy
Paul Pharoah
Nora Pashayan
Kay-Tee Khaw
Janet Stanford
Stephen Thibodeau
Shannon McDonnell
Daniel Schaid
Christiane Maier
Walther Vogel
Manuel Luedeke
Kathleen Herkommer
Adam Kibel
Cezary Cybulski
Dominika Wokolorczyk
Wojciech Kluzniak
Lisa Cannon-Albright
Craig Teerlink
Hermann Brenner
Aida Dieffenbach
Volker Arndt
Jong Park
Thomas Sellers
Hui-Yi Lin
Chavdar Slavov
Radka Kaneva
Vanio Mitev
Jyotsna Batra
Amanda Spurdle
Judith Clements
Manuel Teixeira
Hardev Pandha
Agnieszka Michael
Paula Paulo
Sofia Maia
Andrzej Kierzek
PRACTICAL Consortium
David Conti
Demetrius Albanes
Christine Berg
Sonja Berndt
Daniele Campa
E David Crawford
W Ryan Diver
Susan Gapstur
J Michael Gaziano
Edward Giovannucci
Robert Hoover
David Hunter
Mattias Johansson
Peter Kraft
Loic Le Marchand
Sara Lindström
Carmen Navarro
Kim Overvad
Elio Riboli
Afshan Siddiq
Victoria Stevens
Dimitrios Trichopoulos
Paolo Vineis
Meredith Yeager
Gosia Trynka
Soumya Raychaudhuri
Frederick Schumacher
Alkes Price
Matthew Freedman
Christopher Haiman
Bogdan Pasaniuc
Keywords
Humans
Male
Genetic Predisposition to Disease
Prostatic Neoplasms
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Linkage Disequilibrium
European Continental Ancestry Group
Acetylation
Cell Line, Tumor
Histones
Epigenesis, Genetic
Genetic Loci
African Americans
Inheritance Patterns
Atlases as Topic
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.
Year of Publication
2016
Journal
Nat Commun
Volume
7
Pages
10979
Date Published
2016 Apr 07
ISSN
2041-1723
URL
DOI
10.1038/ncomms10979
PubMed ID
27052111
PubMed Central ID
PMC4829663
Links
Grant list
CA54281 / CA / NCI NIH HHS / United States
CA128978 / CA / NCI NIH HHS / United States
R35 CA197449 / CA / NCI NIH HHS / United States
F32 GM106584 / GM / NIGMS NIH HHS / United States
U10 CA037429 / CA / NCI NIH HHS / United States
C522/A8649 / Cancer Research UK / United Kingdom
1 U19 CA148537-01 / CA / NCI NIH HHS / United States
75466 / Medical Research Council / United Kingdom
C5047/A10692 / Cancer Research UK / United Kingdom
U01 CA194393 / CA / NCI NIH HHS / United States
P30 CA68485 / CA / NCI NIH HHS / United States
UG1 CA189974 / CA / NCI NIH HHS / United States
C8197/A10123 / Cancer Research UK / United Kingdom
R01 CA092447 / CA / NCI NIH HHS / United States
U01 CA188392 / CA / NCI NIH HHS / United States
R01CA056678 / CA / NCI NIH HHS / United States
C490/A10124 / Cancer Research UK / United Kingdom
P30CA042014 / CA / NCI NIH HHS / United States
R01CA082664 / CA / NCI NIH HHS / United States
1U19 CA148065 / CA / NCI NIH HHS / United States
1U19 CA148537 / CA / NCI NIH HHS / United States
R01CA72818 / CA / NCI NIH HHS / United States
C8197/A10865 / Cancer Research UK / United Kingdom
R01 GM107427 / GM / NIGMS NIH HHS / United States
102215 / Wellcome Trust / United Kingdom
R01 CA056678 / CA / NCI NIH HHS / United States
076113 / Wellcome Trust / United Kingdom
CA63464 / CA / NCI NIH HHS / United States
C5047/A8384 / Cancer Research UK / United Kingdom
R01 CA193910 / CA / NCI NIH HHS / United States
C12292/A11174 / Cancer Research UK / United Kingdom
R01 CA128978 / CA / NCI NIH HHS / United States
G0500966 / Medical Research Council / United Kingdom
MC_PC_15018 / Medical Research Council / United Kingdom
R01 CA072818 / CA / NCI NIH HHS / United States
14136 / Cancer Research UK / United Kingdom
U19 CA148537 / CA / NCI NIH HHS / United States
G0401527 / Medical Research Council / United Kingdom
R01 CA063464 / CA / NCI NIH HHS / United States
R01 CA082664 / CA / NCI NIH HHS / United States
C5047/A7357 / Cancer Research UK / United Kingdom
R01 CA054281 / CA / NCI NIH HHS / United States
U01 CA063464 / CA / NCI NIH HHS / United States
P30 CA068485 / CA / NCI NIH HHS / United States
C5047/A3354 / Cancer Research UK / United Kingdom
R01 CA128813 / CA / NCI NIH HHS / United States
G0500966/75466 / Cancer Research UK / United Kingdom
1U19 CA148112 / CA / NCI NIH HHS / United States
R01 GM105857 / GM / NIGMS NIH HHS / United States
C1281/A12014 / Cancer Research UK / United Kingdom
U19 CA148112 / CA / NCI NIH HHS / United States
U01 CA098758 / CA / NCI NIH HHS / United States
C1287/A10710 / Cancer Research UK / United Kingdom
U19 CA148065 / CA / NCI NIH HHS / United States
10119 / Cancer Research UK / United Kingdom
R01CA128813 / CA / NCI NIH HHS / United States
C1287/A10118 / Cancer Research UK / United Kingdom
R01 MH101244 / MH / NIMH NIH HHS / United States
CA098758 / CA / NCI NIH HHS / United States
C16913/A6135 / Cancer Research UK / United Kingdom
R01CA092579 / CA / NCI NIH HHS / United States
R01 CA092579 / CA / NCI NIH HHS / United States
UM1 CA182883 / CA / NCI NIH HHS / United States
R01 CA188392 / CA / NCI NIH HHS / United States
U01 CA164973 / CA / NCI NIH HHS / United States
R37 CA054281 / CA / NCI NIH HHS / United States
P30 CA042014 / CA / NCI NIH HHS / United States
C5047/A15007 / Cancer Research UK / United Kingdom
10124 / Cancer Research UK / United Kingdom

Recent Ó³»­´«Ã½ Publications