Atlas Of Prostate Cancer Heritability In European And African-American Men Pinpoints Tissue-Specific Regulation Alexander Gusev , Huwenbo Shi , Gleb Kichaev , Mark Pomerantz , Fugen Li , Henry W. Long , Sue A. Ingles , Rick A. Kittles , Sara S. Strom , Benjamin A. Rybicki , Barbara Nemesure , William B. Isaacs , Wei Zheng , Curtis A. Pettaway , Edward D. Yeboah , Yao Tettey , Richard B. Biritwum , Andrew A. Adjei , Evelyn Tay , Ann Truelove , Shelley Niwa , Anand P. Chokkalingam , Esther M. John , Adam B. Murphy , Lisa B. Signorello , John Carpten , M. Cristina Leske , Suh-Yuh Wu , Anslem J. M. Hennis , Christine Neslund-Dudas , Ann W. Hsing , Lisa Chu , Phyllis J. Goodman , Eric A. Klein , John S. Witte , Graham Casey , Sam Kaggwa , Michael B. Cook , Daniel O. Stram , William J. Blot , Rosalind A. Eeles , Douglas Easton , Zsofia Kote-Jarai , Ali Amin Al Olama , Sara Benlloch , Kenneth Muir , Graham G. Giles , Melissa C. Southey , Liesel M. Fitzgerald , Henrik Gronberg , Fredrik Wiklund , Markus Aly , Brian E. Henderson , Johanna Schleutker , Tiina Wahlfors , Teuvo L. J. Tammela , Borge G. Nordestgaard , Tim J. Key , Ruth C. Travis , David E. Neal , Jenny L. Donovan , Freddie C. Hamdy , Paul Pharoah , Nora Pashayan , Kay-Tee Khaw , Janet L. Stanford , Stephen N. Thibodeau , Shannon K. Mcdonnell , Daniel J. Schaid , Christiane Maier , Walther Vogel , Manuel Luedeke , Kathleen Herkommer , Adam S. Kibel , Cezary Cybulski , Dominika Wokolorczyk , Wojciech Kluzniak , Lisa Cannon-Albright , Craig Teerlink , Hermann Brenner , Aida K. Dieffenbach , Volker Arndt , Jong Y. Park , Thomas A. Sellers , Hui-Yi Lin , Chavdar Slavov , Radka Kaneva , Vanio Mitev , Jyotsna Batra , Amanda Spurdle , Judith A. Clements , Manuel R. Teixeira , Hardev Pandha , Agnieszka Michael , Paula Paulo , Sofia Maia , Andrzej Kierzek , David V. Conti , Demetrius Albanes , Christine Berg , Sonja I. Berndt , Daniele Campa , E. David Crawford , W. Ryan Diver , Susan M. Gapstur , J. Michael Gaziano , Edward Giovannucci , Robert Hoover , David J. Hunter , Mattias Johansson , Peter Kraft , Loic Le Marchand , Sara Lindstrom , Carmen Navarro , Kim Overvad , Elio Riboli , Afshan Siddiq , Victoria L. Stevens , Dimitrios Trichopoulos , Paolo Vineis , Meredith Yeager , Gosia Trynka , Soumya Raychaudhuri , Frederick R. Schumacher , Alkes L. Price , Matthew L. Freedman , Christopher A. Haiman , Bogdan Pasaniuc , Margaret Cook , Michelle Guy , Koveela Govindasami , Daniel Leongamornlert , Emma J. Sawyer , Rosemary Wilkinson , Edward J. Saunders , Malgorzata Tymrakiewicz , Tokhir Dadaev , Angela Morgan , Cyril Fisher , Steve Hazel , Naomi Livni , Artitaya Lophatananon , John Pedersen , John L. Hopper , Jan Adolfson , Paer Stattin , Jan-Erik Johansson , Carin Cavalli-Bjoerkman , Ami Karlsson , Michael Broms , Anssi Auvinen , Paula Kujala , Liisa Maeaettaenen , Teemu Murtola , Kimmo Taari , Maren Weischer , Sune F. Nielsen , Peter Klarskov , Andreas Roder , Peter Iversen , Hans Wallinder , Sven Gustafsson , Angela Cox , Paul Brown , Anne George , Gemma Marsden , Athene Lane , Michael Davis , Wei Zheng , Lisa B. Signorello , William J. Blot , Lori Tillmans , Shaun Riska , Liang Wang , Antje Rinckleb , Jan Lubiski , Christa Stegmaier , Julio Pow-Sang , Hyun Park , Selina Radlein , Maria Rincon , James Haley , Babu Zachariah , Darina Kachakova , Elenko Popov , Atanaska Mitkova , Aleksandrina Vlahova , Tihomir Dikov , Svetlana Christova , Peter Heathcote , Glenn Wood , Greg Malone , Pamela Saunders , Allison Eckert , Trina Yeadon , Kris Kerr , Angus Collins , Megan Turner , Srilakshmi Srinivasan , Mary-Anne Kedda , Kimberly Alexander , Tracy Omara , Huihai Wu , Rui Henrique , Pedro Pinto , Joana Santos , Joao Barros-Silva NATURE COMMUNICATIONS（2016）
摘要
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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