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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, AUNSPECIFIEDUNSPECIFIED
Shi, HUNSPECIFIEDUNSPECIFIED
Kichaev, GUNSPECIFIEDUNSPECIFIED
Pomerantz, MUNSPECIFIEDUNSPECIFIED
Li, FUNSPECIFIEDUNSPECIFIED
Long, HWUNSPECIFIEDUNSPECIFIED
Ingles, SAUNSPECIFIEDUNSPECIFIED
Kittles, RAUNSPECIFIEDUNSPECIFIED
Strom, SSUNSPECIFIEDUNSPECIFIED
Rybicki, BAUNSPECIFIEDUNSPECIFIED
Nemesure, BUNSPECIFIEDUNSPECIFIED
Isaacs, WBUNSPECIFIEDUNSPECIFIED
Zheng, WUNSPECIFIEDUNSPECIFIED
Pettaway, CAUNSPECIFIEDUNSPECIFIED
Yeboah, EDUNSPECIFIEDUNSPECIFIED
Tettey, YUNSPECIFIEDUNSPECIFIED
Biritwum, RBUNSPECIFIEDUNSPECIFIED
Adjei, AAUNSPECIFIEDUNSPECIFIED
Tay, EUNSPECIFIEDUNSPECIFIED
Truelove, AUNSPECIFIEDUNSPECIFIED
Niwa, SUNSPECIFIEDUNSPECIFIED
Chokkalingam, APUNSPECIFIEDUNSPECIFIED
John, EMUNSPECIFIEDUNSPECIFIED
Murphy, ABUNSPECIFIEDUNSPECIFIED
Signorello, LBUNSPECIFIEDUNSPECIFIED
Carpten, JUNSPECIFIEDUNSPECIFIED
Leske, MCUNSPECIFIEDUNSPECIFIED
Wu, S-YUNSPECIFIEDUNSPECIFIED
Hennis, AJMUNSPECIFIEDUNSPECIFIED
Neslund-Dudas, CUNSPECIFIEDUNSPECIFIED
Hsing, AWUNSPECIFIEDUNSPECIFIED
Chu, LUNSPECIFIEDUNSPECIFIED
Goodman, PJUNSPECIFIEDUNSPECIFIED
Klein, EAUNSPECIFIEDUNSPECIFIED
Witte, JSUNSPECIFIEDUNSPECIFIED
Casey, GUNSPECIFIEDUNSPECIFIED
Kaggwa, SUNSPECIFIEDUNSPECIFIED
Cook, MBUNSPECIFIEDUNSPECIFIED
Stram, DOUNSPECIFIEDUNSPECIFIED
Blot, WJUNSPECIFIEDUNSPECIFIED
Eeles, RAUNSPECIFIEDUNSPECIFIED
Easton, DUNSPECIFIEDUNSPECIFIED
Kote-Jarai, ZUNSPECIFIEDUNSPECIFIED
Al Olama, AAUNSPECIFIEDUNSPECIFIED
Benlloch, SUNSPECIFIEDUNSPECIFIED
Muir, KUNSPECIFIEDUNSPECIFIED
Giles, GGUNSPECIFIEDUNSPECIFIED
Southey, MCUNSPECIFIEDUNSPECIFIED
Fitzgerald, LMUNSPECIFIEDUNSPECIFIED
Gronberg, HUNSPECIFIEDUNSPECIFIED
Wiklund, FUNSPECIFIEDUNSPECIFIED
Aly, MUNSPECIFIEDUNSPECIFIED
Henderson, BEUNSPECIFIEDUNSPECIFIED
Schleutker, JUNSPECIFIEDUNSPECIFIED
Wahlfors, TUNSPECIFIEDUNSPECIFIED
Tammela, TLJUNSPECIFIEDUNSPECIFIED
Nordestgaard, BGUNSPECIFIEDUNSPECIFIED
Key, TJUNSPECIFIEDUNSPECIFIED
Travis, RCUNSPECIFIEDUNSPECIFIED
Neal, DEUNSPECIFIEDUNSPECIFIED
Donovan, JLUNSPECIFIEDUNSPECIFIED
Hamdy, FCUNSPECIFIEDUNSPECIFIED
Pharoah, PUNSPECIFIEDUNSPECIFIED
Pashayan, NUNSPECIFIEDUNSPECIFIED
Khaw, K-TUNSPECIFIEDUNSPECIFIED
Stanford, JLUNSPECIFIEDUNSPECIFIED
Thibodeau, SNUNSPECIFIEDUNSPECIFIED
McDonnell, SKUNSPECIFIEDUNSPECIFIED
Schaid, DJUNSPECIFIEDUNSPECIFIED
Maier, CUNSPECIFIEDUNSPECIFIED
Vogel, WUNSPECIFIEDUNSPECIFIED
Luedeke, MUNSPECIFIEDUNSPECIFIED
Herkommer, KUNSPECIFIEDUNSPECIFIED
Kibel, ASUNSPECIFIEDUNSPECIFIED
Cybulski, CUNSPECIFIEDUNSPECIFIED
Wokolorczyk, DUNSPECIFIEDUNSPECIFIED
Kluzniak, WUNSPECIFIEDUNSPECIFIED
Cannon-Albright, LUNSPECIFIEDUNSPECIFIED
Teerlink, CUNSPECIFIEDUNSPECIFIED
Brenner, HUNSPECIFIEDUNSPECIFIED
Dieffenbach, AKUNSPECIFIEDUNSPECIFIED
Arndt, VUNSPECIFIEDUNSPECIFIED
Park, JYUNSPECIFIEDUNSPECIFIED
Sellers, TAUNSPECIFIEDUNSPECIFIED
Lin, H-YUNSPECIFIEDUNSPECIFIED
Slavov, CUNSPECIFIEDUNSPECIFIED
Kaneva, RUNSPECIFIEDUNSPECIFIED
Mitev, VUNSPECIFIEDUNSPECIFIED
Batra, JUNSPECIFIEDUNSPECIFIED
Spurdle, AUNSPECIFIEDUNSPECIFIED
Clements, JAUNSPECIFIEDUNSPECIFIED
Teixeira, MRUNSPECIFIEDUNSPECIFIED
Pandha, HSUNSPECIFIEDUNSPECIFIED
Michael, AUNSPECIFIEDUNSPECIFIED
Paulo, PUNSPECIFIEDUNSPECIFIED
Maia, SUNSPECIFIEDUNSPECIFIED
Kierzek, AUNSPECIFIEDUNSPECIFIED
Conti, DVUNSPECIFIEDUNSPECIFIED
Albanes, DUNSPECIFIEDUNSPECIFIED
Berg, CUNSPECIFIEDUNSPECIFIED
Berndt, SIUNSPECIFIEDUNSPECIFIED
Campa, DUNSPECIFIEDUNSPECIFIED
Crawford, EDUNSPECIFIEDUNSPECIFIED
Diver, WRUNSPECIFIEDUNSPECIFIED
Gapstur, SMUNSPECIFIEDUNSPECIFIED
Gaziano, JMUNSPECIFIEDUNSPECIFIED
Giovannucci, EUNSPECIFIEDUNSPECIFIED
Hoover, RUNSPECIFIEDUNSPECIFIED
Hunter, DJUNSPECIFIEDUNSPECIFIED
Johansson, MUNSPECIFIEDUNSPECIFIED
Kraft, PUNSPECIFIEDUNSPECIFIED
Le Marchand, LUNSPECIFIEDUNSPECIFIED
Lindstrom, SUNSPECIFIEDUNSPECIFIED
Navarro, CUNSPECIFIEDUNSPECIFIED
Overvad, KUNSPECIFIEDUNSPECIFIED
Riboli, EUNSPECIFIEDUNSPECIFIED
Siddiq, AUNSPECIFIEDUNSPECIFIED
Stevens, VLUNSPECIFIEDUNSPECIFIED
Trichopoulos, DUNSPECIFIEDUNSPECIFIED
Vineis, PUNSPECIFIEDUNSPECIFIED
Yeager, MUNSPECIFIEDUNSPECIFIED
Trynka, GUNSPECIFIEDUNSPECIFIED
Raychaudhuri, SUNSPECIFIEDUNSPECIFIED
Schumacher, FRUNSPECIFIEDUNSPECIFIED
Price, ALUNSPECIFIEDUNSPECIFIED
Freedman, MLUNSPECIFIEDUNSPECIFIED
Haiman, CAUNSPECIFIEDUNSPECIFIED
Pasaniuc, BUNSPECIFIEDUNSPECIFIED
Cook, MUNSPECIFIEDUNSPECIFIED
Guy, MUNSPECIFIEDUNSPECIFIED
Govindasami, KUNSPECIFIEDUNSPECIFIED
Leongamornlert, DUNSPECIFIEDUNSPECIFIED
Sawyer, EJUNSPECIFIEDUNSPECIFIED
Wilkinson, RUNSPECIFIEDUNSPECIFIED
Saunders, EJUNSPECIFIEDUNSPECIFIED
Tymrakiewicz, MUNSPECIFIEDUNSPECIFIED
Dadaev, TUNSPECIFIEDUNSPECIFIED
Morgan, AUNSPECIFIEDUNSPECIFIED
Fischer, CUNSPECIFIEDUNSPECIFIED
Hazel, SUNSPECIFIEDUNSPECIFIED
Livni, NUNSPECIFIEDUNSPECIFIED
Lophatananon, AUNSPECIFIEDUNSPECIFIED
Pedersen, JUNSPECIFIEDUNSPECIFIED
Hopper, JLUNSPECIFIEDUNSPECIFIED
Adolfson, JUNSPECIFIEDUNSPECIFIED
Stattin, PUNSPECIFIEDUNSPECIFIED
Johansson, J-EUNSPECIFIEDUNSPECIFIED
Cavalli-Bjoerkman, CUNSPECIFIEDUNSPECIFIED
Karlsson, AUNSPECIFIEDUNSPECIFIED
Broms, MUNSPECIFIEDUNSPECIFIED
Auvinen, AUNSPECIFIEDUNSPECIFIED
Kujala, PUNSPECIFIEDUNSPECIFIED
Maeaettaenen, LUNSPECIFIEDUNSPECIFIED
Murtola, TUNSPECIFIEDUNSPECIFIED
Taari, KUNSPECIFIEDUNSPECIFIED
Weischer, MUNSPECIFIEDUNSPECIFIED
Nielsen, SFUNSPECIFIEDUNSPECIFIED
Klarskov, PUNSPECIFIEDUNSPECIFIED
Roder, AUNSPECIFIEDUNSPECIFIED
Iversen, PUNSPECIFIEDUNSPECIFIED
Wallinder, HUNSPECIFIEDUNSPECIFIED
Signorello, LBUNSPECIFIEDUNSPECIFIED
Blot, WJUNSPECIFIEDUNSPECIFIED
Tillmans, LUNSPECIFIEDUNSPECIFIED
Riska, SUNSPECIFIEDUNSPECIFIED
Wang, LUNSPECIFIEDUNSPECIFIED
Rinckleb, AUNSPECIFIEDUNSPECIFIED
Lubiski, JUNSPECIFIEDUNSPECIFIED
Stegmaier, CUNSPECIFIEDUNSPECIFIED
Pow-Sang, JUNSPECIFIEDUNSPECIFIED
Park, HUNSPECIFIEDUNSPECIFIED
Radlein, SUNSPECIFIEDUNSPECIFIED
Rincon, MUNSPECIFIEDUNSPECIFIED
Haley, JUNSPECIFIEDUNSPECIFIED
Zachariah, BUNSPECIFIEDUNSPECIFIED
Kachakova, DUNSPECIFIEDUNSPECIFIED
Popov, EUNSPECIFIEDUNSPECIFIED
Mitkova, AUNSPECIFIEDUNSPECIFIED
Vlahova, AUNSPECIFIEDUNSPECIFIED
Dikov, TUNSPECIFIEDUNSPECIFIED
Christova, SUNSPECIFIEDUNSPECIFIED
Heathcote, PUNSPECIFIEDUNSPECIFIED
Wood, GUNSPECIFIEDUNSPECIFIED
Malone, GUNSPECIFIEDUNSPECIFIED
Saunders, KUNSPECIFIEDUNSPECIFIED
Eckert, AUNSPECIFIEDUNSPECIFIED
Yeadon, TUNSPECIFIEDUNSPECIFIED
Kerr, KUNSPECIFIEDUNSPECIFIED
Collins, AUNSPECIFIEDUNSPECIFIED
Turner, MUNSPECIFIEDUNSPECIFIED
Srinivasan, SUNSPECIFIEDUNSPECIFIED
Kedda, M-AUNSPECIFIEDUNSPECIFIED
Alexander, KUNSPECIFIEDUNSPECIFIED
Omara, TUNSPECIFIEDUNSPECIFIED
Wu, HUNSPECIFIEDUNSPECIFIED
Henrique, RUNSPECIFIEDUNSPECIFIED
Pinto, PUNSPECIFIEDUNSPECIFIED
Santos, JUNSPECIFIEDUNSPECIFIED
Barros-Silva, JUNSPECIFIEDUNSPECIFIED
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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