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 & 108 others 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

Research output: Contribution to journalArticle

19 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 (US)
Article number10979
JournalNature Communications
Volume7
DOIs
StatePublished - Apr 7 2016

Fingerprint

Atlases
African Americans
Prostatic Neoplasms
cancer
Tissue
cultured cells
Cells
Polymorphism
Epigenomics
Cell Line
Single Nucleotide Polymorphism
polymorphism
nucleotides
Prostate
Nucleotides
Acetylation
Genome-Wide Association Study
acetylation
annotations
genome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

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

In: Nature Communications, Vol. 7, 10979, 07.04.2016.

Research output: Contribution to journalArticle

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
Gusev, Alexander ; Shi, Huwenbo ; Kichaev, Gleb ; Pomerantz, Mark ; Li, Fugen ; Long, Henry W. ; Ingles, Sue A. ; Kittles, Rick A. ; Strom, Sara S. ; Rybicki, Benjamin A. ; Nemesure, Barbara ; Isaacs, William B. ; Zheng, Wei ; Pettaway, Curtis A. ; Yeboah, Edward D. ; Tettey, Yao ; Biritwum, Richard B. ; Adjei, Andrew A. ; Tay, Evelyn ; Truelove, Ann ; Niwa, Shelley ; Chokkalingam, Anand P. ; John, Esther M. ; Murphy, Adam B. ; Signorello, Lisa B. ; Carpten, John ; Leske, M. Cristina ; Wu, Suh Yuh ; Hennis, Anslem J M ; Neslund-Dudas, Christine ; Hsing, Ann W. ; Chu, Lisa ; Goodman, Phyllis J. ; Klein, Eric A. ; Witte, John S. ; Casey, Graham ; Kaggwa, Sam ; Cook, Michael B. ; Stram, Daniel O. ; Blot, William J. ; Eeles, Rosalind A. ; Easton, Douglas ; Kote-Jarai, Zsofia ; Al Olama, Ali Amin ; Benlloch, Sara ; Muir, Kenneth ; Giles, Graham G. ; Southey, Melissa C. ; Fitzgerald, Liesel M. ; Gronberg, Henrik ; Wiklund, Fredrik ; Aly, Markus ; Henderson, Brian E. ; Schleutker, Johanna ; Wahlfors, Tiina ; Tammela, Teuvo L J ; Nordestgaard, Børge G. ; Key, Tim J. ; Travis, Ruth C. ; Neal, David E. ; Donovan, Jenny L. ; Hamdy, Freddie C. ; Pharoah, Paul ; Pashayan, Nora ; Khaw, Kay Tee ; Stanford, Janet L. ; Thibodeau, Stephen N ; McDonnell, Shannon K. ; Schaid, Daniel J ; Maier, Christiane ; Vogel, Walther ; Luedeke, Manuel ; Herkommer, Kathleen ; Kibel, Adam S. ; Cybulski, Cezary ; Wokolorczyk, Dominika ; Kluzniak, Wojciech ; Cannon-Albright, Lisa ; Teerlink, Craig ; Brenner, Hermann ; Dieffenbach, Aida K. ; Arndt, Volker ; Park, Jong Y. ; Sellers, Thomas A. ; Lin, Hui Yi ; Slavov, Chavdar ; Kaneva, Radka ; Mitev, Vanio ; Batra, Jyotsna ; Spurdle, Amanda ; Clements, Judith A. ; Teixeira, Manuel R. ; Pandha, Hardev ; Michael, Agnieszka ; Paulo, Paula ; Maia, Sofia ; Kierzek, Andrzej ; Conti, David V. ; Albanes, Demetrius ; Berg, Christine ; Berndt, Sonja I. ; Campa, Daniele ; Crawford, E. David ; Diver, W. Ryan ; Gapstur, Susan M. ; Gaziano, J. Michael ; Giovannucci, Edward ; Hoover, Robert ; Hunter, David J. ; Johansson, Mattias ; Kraft, Peter ; Le Marchand, Loic ; Lindström, Sara ; Navarro, Carmen ; Overvad, Kim ; Riboli, Elio ; Siddiq, Afshan ; Stevens, Victoria L. ; Trichopoulos, Dimitrios ; Vineis, Paolo ; Yeager, Meredith ; Trynka, Gosia ; Raychaudhuri, Soumya ; Schumacher, Frederick R. ; Price, Alkes L. ; Freedman, Matthew L. ; Haiman, Christopher A. ; Pasaniuc, Bogdan. / Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation. In: Nature Communications. 2016 ; Vol. 7.
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AU - Truelove, Ann

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AU - Chokkalingam, Anand P.

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AU - Wu, Suh Yuh

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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

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AU - Riboli, Elio

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AU - Trynka, Gosia

AU - Raychaudhuri, Soumya

AU - Schumacher, Frederick R.

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AU - Haiman, Christopher A.

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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.

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