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 TrueloveShelley Niwa, Anand P. Chokkalingam, Esther M. John, Adam B. Murphy, Lisa B. Signorello, John D. 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 F 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 D P 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 Karina Dieffenbach, Volker Arndt, Jong Y. Park, Thomas A Sellers, Hui-Yi Lin Lin, Chavdar Slavov, Radka P. Kaneva, Vanio Mitev, Jyotsna Batra, Amanda B Spurdle, Judith A. Clements, Manuel R Teixeira, Hardev S Pandha, Agnieszka Michael, Paula Paulo, Sofia Maia, Andrzej Kierzek, David V Conti, Demetrius Albanes, Christine D Berg, Sonja I. Berndt, Daniele Campa, E David Crawford, William Ryan Diver, Susan M. Gapstur, J. Michael Gaziano, Edward Giovannucci, Robert N Hoover, David J. Hunter, Mattias Johansson, Peter Kraft, Loic Le Marchand, Sara Lindström, Carmen Navarro, Kim Overvad, Elio B 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, The PRACTICAL consortium

Research output: Contribution to journalArticleResearchpeer-review

31 Citations (Scopus)

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.

Original languageEnglish
Article number10979
Number of pages13
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 7 Apr 2016
Externally publishedYes

Cite this