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

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Gusev, A and Shi, H and Kichaev, G and Pomerantz, M and Li, F and Long, HW and Ingles, SA and Kittles, RA and Strom, SS and Rybicki, BA and Nemesure, B and Isaacs, WB and Zheng, W and Pettaway, CA and Yeboah, ED and Tettey, Y and Biritwum, RB and Adjei, AA and Tay, E and Truelove, A and Niwa, S and Chokkalingam, AP and John, EM and Murphy, AB and Signorello, LB and Carpten, J and Leske, Mc and Wu, S-Y and Hennis, AJM and Neslund-Dudas, C and Hsing, AW and Chu, L and Goodman, PJ and Klein, EA and Witte, JS and Casey, G and Kaggwa, S and Cook, MB and Stram, DO and Blot, WJ and Eeles, RA and Easton, D and Kote-Jarai, Z and Al Olama, AA and Benlloch, S and Muir, K and Giles, GG and Southey, MC and Fitzgerald, LM and Gronberg, H and Wiklund, F and Aly, M and Henderson, BE and Schleutker, J and Wahlfors, T and Tammela, TLJ and Nordestgaard, BG and Key, TJ and Travis, RC and Neal, DE and Donovan, JL and Hamdy, FC and Pharoah, P and Pashayan, N and Khaw, K-T and Stanford, JL and Thibodeau, SN and McDonnell, SK and Schaid, DJ and Maier, C and Vogel, W and Luedeke, M and Herkommer, K and Kibel, AS and Cybulski, C and Wokolorczyk, D and Kluzniak, W and Cannon-Albright, L and Teerlink, C and Brenner, H and Dieffenbach, AK and Arndt, V and Park, JY and Sellers, TA and Lin, H-Y and Slavov, C and Kaneva, R and Mitev, V and Batra, J and Spurdle, A and Clements, JA and Teixeira, MR and Pandha, H and Michael, A and Paulo, P and Maia, S and Kierzek, A and Conti, DV and Albanes, D and Berg, C and Berndt, SJ and Campa, D and Crawford, ED and Diver, WR and Gapstur, SM and Gaziano, JM and Giovannucci, E and Hoover, R and Hunter, DJ and Johansson, M and Kraft, P and Le Marchand, L and Lindstrom, S and Navarro, C and Overvad, K and Riboli, E and Siddiq, A and Stevens, VL and Trichopoulos, D and Vineis, P and Yeager, M and Trynka, G and Raychaudhuri, S and Schumacher, FR and Price, AL and Freedman, ML and Haiman, CA and Pasaniuc, B and The PRACTICAL Consortium, Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation, Nature communications, 7 Article 10979. ISSN 2041-1723 (2016) [Refereed Article]


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Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1038/ncomms10979

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 Details

Item Type:Refereed Article
Keywords:prostate cancer
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Cancer Genetics
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Fitzgerald, LM (Dr Liesel Fitzgerald)
ID Code:110624
Year Published:2016
Web of Science® Times Cited:11
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-08-05
Last Modified:2017-11-06
Downloads:58 View Download Statistics

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