A1 Refereed original research article in a scientific journal
Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
Authors: 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 SY, 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 KT, 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 HY, Slavov C, Kaneva R, Mitev V, Batra J, Spurdle A, Clements JA, Teixeira MR, Pandha H, 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, Fisher C, Hazel S, Livni N, Lophatananon A, Pedersen J, Hopper JL, Adolfson J, Stattin P, Johansson JE, 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, Gustafsson S, Cox A, Brown P, George A, Marsden G, Lane A, Davis M, Zheng W, 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 P, Eckert A, Yeadon T, Kerr K, Collins A, Turner M, Srinivasan S, Kedda MA, Alexander K, Omara T, Wu HH, Henrique R, Pinto P, Santos J, Barros-Silva J
Publisher: NATURE PUBLISHING GROUP
Publication year: 2016
Journal: Nature Communications
Journal name in source: NATURE COMMUNICATIONS
Journal acronym: NAT COMMUN
Article number: ARTN 10979
Volume: 7
Number of pages: 13
ISSN: 2041-1723
DOI: https://doi.org/10.1038/ncomms10979
Although genome-wide association studies have identified over 100 risk loci that explain similar to 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.
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