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

Authors:
Ali Amin Olama, PhD
Ali Amin Olama, PhD
University Of Cambridge
Dr.
Cambridge | United Kingdom
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 Børge 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 Lindström 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

Nat Commun 2016 Apr 7;7:10979. Epub 2016 Apr 7.

Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, California 90095, USA.

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.

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http://dx.doi.org/10.1038/ncomms10979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829663PMC
April 2016
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