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; 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

doi:10.1038/ncomms10979

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, 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

Stony Brook University

Harvard University
Broad Institute
University of California at Los Angeles
Dana-Farber Cancer Institute
University of Southern California
University of Arizona
University of Texas MD Anderson Cancer Center
Henry Ford Health System
Johns Hopkins University
Vanderbilt University
University of Texas Health Science Center at Houston
Korle Bu Teaching Hospital
University of Ghana
Westat
University of California at Berkeley
Cancer Prevention Institute of California
Stanford University
Northwestern University
International Epidemiology Institute
Translational Genomics Research Institute
Stony Brook University
The University of the West Indies
Fred Hutchinson Cancer Research Center
Cleveland Clinic Foundation
University of California at San Francisco
Makerere University
National Institutes of Health
The Institute of Cancer Research
Royal Marsden NHS Foundation Trust
University of Cambridge
University of Manchester
University of Warwick
Cancer Council Victoria
University of Melbourne
Karolinska Institutet
Stockholm County Council
University of Turku
Tampere University
University of Copenhagen
University of Oxford
Cancer Research UK Cambridge Institute
University of Bristol
Aarhus University
University College London
University of Washington
Mayo Clinic Rochester, MN
Ulm University
Technical University of Munich
Brigham and Women’s Hospital
Pomeranian Medical University in Szczecin
University of Utah
VA Medical Center
German Cancer Research Center
Moffitt Cancer Center
Medical University Sofia
Queensland University of Technology
Queensland Institute of Medical Research
Instituto Português de Oncologia do Porto Francisco Gentil E.P.E.
University of Porto
University of Surrey
University of Colorado Denver
American Cancer Society
International Agency for Research on Cancer
Umeå University
University of Hawai'i at Mānoa
Regional Health Authority
CIBER Epidemiología y Salud Pública (CIBERESP)
Imperial College London
Academy of Athens
Helenic Health Foundation
HuGeF Foundation
Wellcome Trust

Research output: Contribution to journal › Article › peer-review

45 Scopus citations

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 language	English
Article number	10979
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10979
State	Published - Apr 7 2016

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10.1038/ncomms10979

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Gusev, A., Shi, H., Kichaev, G., Pomerantz, M., Li, F., Long, H. W., Ingles, S. A., Kittles, R. A., Strom, S. S., Rybicki, B. A., Nemesure, B., Isaacs, W. B., Zheng, W., Pettaway, C. A., Yeboah, E. D., Tettey, Y., Biritwum, R. B., Adjei, A. A., Tay, E., ... Pasaniuc, B. (2016). Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation. Nature Communications, 7, Article 10979. https://doi.org/10.1038/ncomms10979

@article{1cc7668a1f494cdbbb90e1c2aca6a11b,

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

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.",

author = "Alexander Gusev and Huwenbo Shi and Gleb Kichaev and Mark Pomerantz and Fugen Li and Long, \{Henry W.\} and Ingles, \{Sue A.\} and Kittles, \{Rick A.\} and Strom, \{Sara S.\} and Rybicki, \{Benjamin A.\} and Barbara Nemesure and Isaacs, \{William B.\} and Wei Zheng and Pettaway, \{Curtis A.\} and Yeboah, \{Edward D.\} and Yao Tettey and Biritwum, \{Richard B.\} and Adjei, \{Andrew A.\} and Evelyn Tay and Ann Truelove and Shelley Niwa and Chokkalingam, \{Anand P.\} and John, \{Esther M.\} and Murphy, \{Adam B.\} and Signorello, \{Lisa B.\} and John Carpten and Leske, \{M. Cristina\} and Wu, \{Suh Yuh\} and Hennis, \{Anslem J.M.\} and Christine Neslund-Dudas and Hsing, \{Ann W.\} and Lisa Chu and Goodman, \{Phyllis J.\} and Klein, \{Eric A.\} and Witte, \{John S.\} and Graham Casey and Sam Kaggwa and Cook, \{Michael B.\} and Stram, \{Daniel O.\} and Blot, \{William J.\} and Eeles, \{Rosalind A.\} and Douglas Easton and Zsofia Kote-Jarai and \{Al Olama\}, \{Ali Amin\} and Sara Benlloch and Kenneth Muir and Giles, \{Graham G.\} and Southey, \{Melissa C.\} and Fitzgerald, \{Liesel M.\} and Henrik Gronberg and Fredrik Wiklund and Markus Aly and Henderson, \{Brian E.\} and Johanna Schleutker and Tiina Wahlfors and Tammela, \{Teuvo L.J.\} and Nordestgaard, \{B{\o}rge G.\} and Key, \{Tim J.\} and Travis, \{Ruth C.\} and Neal, \{David E.\} and Donovan, \{Jenny L.\} and Hamdy, \{Freddie C.\} and Paul Pharoah and Nora Pashayan and Khaw, \{Kay Tee\} and Stanford, \{Janet L.\} and Thibodeau, \{Stephen N.\} and McDonnell, \{Shannon K.\} and Schaid, \{Daniel J.\} and Christiane Maier and Walther Vogel and Manuel Luedeke and Kathleen Herkommer and Kibel, \{Adam S.\} and Cezary Cybulski and Dominika Wokolorczyk and Wojciech Kluzniak and Lisa Cannon-Albright and Craig Teerlink and Hermann Brenner and Dieffenbach, \{Aida K.\} and Volker Arndt and Park, \{Jong Y.\} and Sellers, \{Thomas A.\} and Lin, \{Hui Yi\} and Chavdar Slavov and Radka Kaneva and Vanio Mitev and Jyotsna Batra and Amanda Spurdle and Clements, \{Judith A.\} and Teixeira, \{Manuel R.\} and Hardev Pandha and Agnieszka Michael and Paula Paulo and Sofia Maia and Andrzej Kierzek and Conti, \{David V.\} and Demetrius Albanes and Christine Berg and Berndt, \{Sonja I.\} and Daniele Campa and Crawford, \{E. David\} and Diver, \{W. Ryan\} and Gapstur, \{Susan M.\} and Gaziano, \{J. Michael\} and Edward Giovannucci and Robert Hoover and Hunter, \{David J.\} and Mattias Johansson and Peter Kraft and \{Le Marchand\}, Loic and Sara Lindstr{\"o}m and Carmen Navarro and Kim Overvad and Elio Riboli and Afshan Siddiq and Stevens, \{Victoria L.\} and Dimitrios Trichopoulos and Paolo Vineis and Meredith Yeager and Gosia Trynka and Soumya Raychaudhuri and Schumacher, \{Frederick R.\} and Price, \{Alkes L.\} and Freedman, \{Matthew L.\} and Haiman, \{Christopher A.\} and Bogdan Pasaniuc",

year = "2016",

month = apr,

day = "7",

doi = "10.1038/ncomms10979",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

}

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, Lindström, 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 2016, 'Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation', Nature Communications, vol. 7, 10979. https://doi.org/10.1038/ncomms10979

TY - JOUR

T1 - Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

AU - Gusev, Alexander

AU - Shi, Huwenbo

AU - Kichaev, Gleb

AU - Pomerantz, Mark

AU - Li, Fugen

AU - Long, Henry W.

AU - Ingles, Sue A.

AU - Kittles, Rick A.

AU - Strom, Sara S.

AU - Rybicki, Benjamin A.

AU - Nemesure, Barbara

AU - Isaacs, William B.

AU - Zheng, Wei

AU - Pettaway, Curtis A.

AU - Yeboah, Edward D.

AU - Tettey, Yao

AU - Biritwum, Richard B.

AU - Adjei, Andrew A.

AU - Tay, Evelyn

AU - Truelove, Ann

AU - Niwa, Shelley

AU - Chokkalingam, Anand P.

AU - John, Esther M.

AU - Murphy, Adam B.

AU - Signorello, Lisa B.

AU - Carpten, John

AU - Leske, M. Cristina

AU - Wu, Suh Yuh

AU - Hennis, Anslem J.M.

AU - Neslund-Dudas, Christine

AU - Hsing, Ann W.

AU - Chu, Lisa

AU - Goodman, Phyllis J.

AU - Klein, Eric A.

AU - Witte, John S.

AU - Casey, Graham

AU - Kaggwa, Sam

AU - Cook, Michael B.

AU - Stram, Daniel O.

AU - Blot, William J.

AU - Eeles, Rosalind A.

AU - Easton, Douglas

AU - Kote-Jarai, Zsofia

AU - Al Olama, Ali Amin

AU - Benlloch, Sara

AU - Muir, Kenneth

AU - Giles, Graham G.

AU - Southey, Melissa C.

AU - Fitzgerald, Liesel M.

AU - Gronberg, Henrik

AU - Wiklund, Fredrik

AU - Aly, Markus

AU - Henderson, Brian E.

AU - Schleutker, Johanna

AU - Wahlfors, Tiina

AU - Tammela, Teuvo L.J.

AU - Nordestgaard, Børge G.

AU - Key, Tim J.

AU - Travis, Ruth C.

AU - Neal, David E.

AU - Donovan, Jenny L.

AU - Hamdy, Freddie C.

AU - Pharoah, Paul

AU - Pashayan, Nora

AU - Khaw, Kay Tee

AU - Stanford, Janet L.

AU - Thibodeau, Stephen N.

AU - McDonnell, Shannon K.

AU - Schaid, Daniel J.

AU - Maier, Christiane

AU - Vogel, Walther

AU - Luedeke, Manuel

AU - Herkommer, Kathleen

AU - Kibel, Adam S.

AU - Cybulski, Cezary

AU - Wokolorczyk, Dominika

AU - Kluzniak, Wojciech

AU - Cannon-Albright, Lisa

AU - Teerlink, Craig

AU - Brenner, Hermann

AU - Dieffenbach, Aida K.

AU - Arndt, Volker

AU - Park, Jong Y.

AU - Sellers, Thomas A.

AU - Lin, Hui Yi

AU - Slavov, Chavdar

AU - Kaneva, Radka

AU - Mitev, Vanio

AU - Batra, Jyotsna

AU - Spurdle, Amanda

AU - Clements, Judith A.

AU - Teixeira, Manuel R.

AU - Pandha, Hardev

AU - Michael, Agnieszka

AU - Paulo, Paula

AU - Maia, Sofia

AU - Kierzek, Andrzej

AU - Conti, David V.

AU - Albanes, Demetrius

AU - Berg, Christine

AU - Berndt, Sonja I.

AU - Campa, Daniele

AU - Crawford, E. David

AU - Diver, W. Ryan

AU - Gapstur, Susan M.

AU - Gaziano, J. Michael

AU - Giovannucci, Edward

AU - Hoover, Robert

AU - Hunter, David J.

AU - Johansson, Mattias

AU - Kraft, Peter

AU - Le Marchand, Loic

AU - Lindström, Sara

AU - Navarro, Carmen

AU - Overvad, Kim

AU - Riboli, Elio

AU - Siddiq, Afshan

AU - Stevens, Victoria L.

AU - Trichopoulos, Dimitrios

AU - Vineis, Paolo

AU - Yeager, Meredith

AU - Trynka, Gosia

AU - Raychaudhuri, Soumya

AU - Schumacher, Frederick R.

AU - Price, Alkes L.

AU - Freedman, Matthew L.

AU - Haiman, Christopher A.

AU - Pasaniuc, Bogdan

PY - 2016/4/7

Y1 - 2016/4/7

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84963635486

U2 - 10.1038/ncomms10979

DO - 10.1038/ncomms10979

M3 - Article

C2 - 27052111

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 10979

ER -

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

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