Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.
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Date
2016-04-07Author
Gusev, A
Shi, H
Kichaev, G
Pomerantz, M
Li, F
Long, HW
Ingles, SA
Kittles, RA
Strom, SS
Rybicki, BA
Nemesure, B
Isaacs, WB
Zheng, W
Pettaway, CA
Yeboah, ED
Tettey, Y
Biritwum, RB
Adjei, AA
Tay, E
Truelove, A
Niwa, S
Chokkalingam, AP
John, EM
Murphy, AB
Signorello, LB
Carpten, J
Leske, MC
Wu, S-Y
Hennis, AJM
Neslund-Dudas, C
Hsing, AW
Chu, L
Goodman, PJ
Klein, EA
Witte, JS
Casey, G
Kaggwa, S
Cook, MB
Stram, DO
Blot, WJ
Eeles, RA
Easton, D
Kote-Jarai, Z
Al Olama, AA
Benlloch, S
Muir, K
Giles, GG
Southey, MC
Fitzgerald, LM
Gronberg, H
Wiklund, F
Aly, M
Henderson, BE
Schleutker, J
Wahlfors, T
Tammela, TLJ
Nordestgaard, BG
Key, TJ
Travis, RC
Neal, DE
Donovan, JL
Hamdy, FC
Pharoah, P
Pashayan, N
Khaw, K-T
Stanford, JL
Thibodeau, SN
McDonnell, SK
Schaid, DJ
Maier, C
Vogel, W
Luedeke, M
Herkommer, K
Kibel, AS
Cybulski, C
Wokolorczyk, D
Kluzniak, W
Cannon-Albright, L
Teerlink, C
Brenner, H
Dieffenbach, AK
Arndt, V
Park, JY
Sellers, TA
Lin, H-Y
Slavov, C
Kaneva, R
Mitev, V
Batra, J
Spurdle, A
Clements, JA
Teixeira, MR
Pandha, H
Michael, A
Paulo, P
Maia, S
Kierzek, A
PRACTICAL consortium,
Conti, DV
Albanes, D
Berg, C
Berndt, SI
Campa, D
Crawford, ED
Diver, WR
Gapstur, SM
Gaziano, JM
Giovannucci, E
Hoover, R
Hunter, DJ
Johansson, M
Kraft, P
Le Marchand, L
Lindström, S
Navarro, C
Overvad, K
Riboli, E
Siddiq, A
Stevens, VL
Trichopoulos, D
Vineis, P
Yeager, M
Trynka, G
Raychaudhuri, S
Schumacher, FR
Price, AL
Freedman, ML
Haiman, CA
Pasaniuc, B
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
PRACTICAL consortium
Cell Line, Tumor
Humans
Prostatic Neoplasms
Genetic Predisposition to Disease
Histones
Epigenesis, Genetic
Acetylation
Inheritance Patterns
Linkage Disequilibrium
Polymorphism, Single Nucleotide
African Americans
European Continental Ancestry Group
Male
Atlases as Topic
Genome-Wide Association Study
Genetic Loci
Research team
Oncogenetics
Language
eng
Date accepted
2016-02-03
License start date
2016-04-07
Citation
Nature communications, 2016, 7 pp. 10979 - ?
Publisher
NATURE PUBLISHING GROUP