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

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, HS, Michael, A, Paulo, P, Maia, S, Kierzek, A, 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, Lindstrom, 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, Cook, M, Guy, M, Govindasami, K, Leongamornlert, D, Sawyer, EJ, Wilkinson, R, Saunders, EJ, Tymrakiewicz, M, Dadaev, T, Morgan, A, Fischer, C, Hazel, S, Livni, N, Lophatananon, A, Pedersen, J, Hopper, JL, Adolfson, J, Stattin, P, Johansson, J-E, Cavalli-Bjoerkman, C, Karlsson, A, Broms, M, Auvinen, A, Kujala, P, Maeaettaenen, L, Murtola, T, Taari, K, Weischer, M, Nielsen, SF, Klarskov, P, Roder, A, Iversen, P, Wallinder, H, Signorello, LB, Blot, WJ, Tillmans, L, Riska, S, Wang, L, Rinckleb, A, Lubiski, J, Stegmaier, C, Pow-Sang, J, Park, H, Radlein, S, Rincon, M, Haley, J, Zachariah, B, Kachakova, D, Popov, E, Mitkova, A, Vlahova, A, Dikov, T, Christova, S, Heathcote, P, Wood, G, Malone, G, Saunders, K, Eckert, A, Yeadon, T, Kerr, K, Collins, A, Turner, M, Srinivasan, S, Kedda, M-A, Alexander, K, Omara, T, Wu, H, Henrique, R, Pinto, P, Santos, J and Barros-Silva, J (2016) Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation Nature Communications, 7.

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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.

Item Type: Article
Subjects : Medical Science
Divisions : Faculty of Health and Medical Sciences
Authors :
NameEmailORCID
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, HS
Michael, A
Paulo, P
Maia, S
Kierzek, A
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
Lindstrom, 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
Cook, M
Guy, M
Govindasami, K
Leongamornlert, D
Sawyer, EJ
Wilkinson, R
Saunders, EJ
Tymrakiewicz, M
Dadaev, T
Morgan, A
Fischer, C
Hazel, S
Livni, N
Lophatananon, A
Pedersen, J
Hopper, JL
Adolfson, J
Stattin, P
Johansson, J-E
Cavalli-Bjoerkman, C
Karlsson, A
Broms, M
Auvinen, A
Kujala, P
Maeaettaenen, L
Murtola, T
Taari, K
Weischer, M
Nielsen, SF
Klarskov, P
Roder, A
Iversen, P
Wallinder, H
Signorello, LB
Blot, WJ
Tillmans, L
Riska, S
Wang, L
Rinckleb, A
Lubiski, J
Stegmaier, C
Pow-Sang, J
Park, H
Radlein, S
Rincon, M
Haley, J
Zachariah, B
Kachakova, D
Popov, E
Mitkova, A
Vlahova, A
Dikov, T
Christova, S
Heathcote, P
Wood, G
Malone, G
Saunders, K
Eckert, A
Yeadon, T
Kerr, K
Collins, A
Turner, M
Srinivasan, S
Kedda, M-A
Alexander, K
Omara, T
Wu, H
Henrique, R
Pinto, P
Santos, J
Barros-Silva, J
Date : 7 April 2016
Identification Number : 10.1038/ncomms10979
Copyright Disclaimer : © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Uncontrolled Keywords : Biological sciences, Cancer, Genetics, Genome-wide association studies, Prostate cancer, Population genetics
Depositing User : Symplectic Elements
Date Deposited : 22 Nov 2016 11:48
Last Modified : 31 Oct 2017 18:57
URI: http://epubs.surrey.ac.uk/id/eprint/812929

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