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 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

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 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 journal › Article › Research › peer-review

42 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 language	English
Article number	10979
Number of pages	13
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10979
Publication status	Published - 7 Apr 2016
Externally published	Yes

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10.1038/ncomms10979Licence: CC BY

117350680-oaFinal published version, 911 KBLicence: CC BY

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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., ... The PRACTICAL consortium (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

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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 Carpten, {John D.} 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 Easton, {Douglas F} 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 Pharoah, {Paul D P} and Nora Pashayan and Kay-Tee Khaw 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 Karina} and Volker Arndt and Park, {Jong Y.} and Sellers, {Thomas A} and Lin, {Hui-Yi Lin} and Chavdar Slavov and Kaneva, {Radka P.} and Vanio Mitev and Jyotsna Batra and Spurdle, {Amanda B} and Clements, {Judith A.} and Teixeira, {Manuel R} and Pandha, {Hardev S} and Agnieszka Michael and Paula Paulo and Sofia Maia and Andrzej Kierzek and Conti, {David V} and Demetrius Albanes and Berg, {Christine D} and Berndt, {Sonja I.} and Daniele Campa and Crawford, {E David} and Diver, {William Ryan} and Gapstur, {Susan M.} and Gaziano, {J. Michael} and Edward Giovannucci and Hoover, {Robert N} 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 Riboli, {Elio B} 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 and {The PRACTICAL consortium}",

year = "2016",

month = apr,

day = "7",

doi = "10.1038/ncomms10979",

language = "English",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

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, JD, 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, DF, 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, PDP, Pashayan, N, Khaw, K-T, 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, H-YL, Slavov, C, Kaneva, RP, Mitev, V, Batra, J, Spurdle, AB, Clements, JA, Teixeira, MR, Pandha, HS, Michael, A, Paulo, P, Maia, S, Kierzek, A, Conti, DV, Albanes, D, Berg, CD, Berndt, SI, Campa, D, Crawford, ED, Diver, WR, Gapstur, SM, Gaziano, JM, Giovannucci, E, Hoover, RN, Hunter, DJ, Johansson, M, Kraft, P, Le Marchand, L, Lindström, S, Navarro, C, Overvad, K, Riboli, EB, Siddiq, A, Stevens, VL, Trichopoulos, D, Vineis, P, Yeager, M, Trynka, G, Raychaudhuri, S, Schumacher, FR, Price, AL, Freedman, ML, Haiman, CA, Pasaniuc, B & The PRACTICAL consortium 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 D.

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 F

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 D P

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 Karina

AU - Arndt, Volker

AU - Park, Jong Y.

AU - Sellers, Thomas A

AU - Lin, Hui-Yi Lin

AU - Slavov, Chavdar

AU - Kaneva, Radka P.

AU - Mitev, Vanio

AU - Batra, Jyotsna

AU - Spurdle, Amanda B

AU - Clements, Judith A.

AU - Teixeira, Manuel R

AU - Pandha, Hardev S

AU - Michael, Agnieszka

AU - Paulo, Paula

AU - Maia, Sofia

AU - Kierzek, Andrzej

AU - Conti, David V

AU - Albanes, Demetrius

AU - Berg, Christine D

AU - Berndt, Sonja I.

AU - Campa, Daniele

AU - Crawford, E David

AU - Diver, William Ryan

AU - Gapstur, Susan M.

AU - Gaziano, J. Michael

AU - Giovannucci, Edward

AU - Hoover, Robert N

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 B

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

AU - The PRACTICAL consortium

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 - http://www.scopus.com/inward/record.url?scp=84963635486&partnerID=8YFLogxK

U2 - 10.1038/ncomms10979

DO - 10.1038/ncomms10979

M3 - Article

C2 - 27052111

AN - SCOPUS:84963635486

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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