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; The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium; Jyotsna Batra

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
, The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium
, Jyotsna Batra

^*Corresponding author for this work

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

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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
Pages (from-to)	1-13
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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Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulationFinal 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., The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, & Batra, J. (2016). Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation. Nature Communications, 7, 1-13. Article 10979. https://doi.org/10.1038/ncomms10979

@article{5530f48fa62b40ab8cff7a03fce40be8,

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 \{The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium\} 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",

year = "2016",

month = apr,

day = "7",

doi = "10.1038/ncomms10979",

language = "English",

volume = "7",

pages = "1--13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

Gusev, A, Shi, H, Kichaev, G, Pomerantz, M, Li, F, Long, HW, Ingles, SA, Kittles, RA, Strom, SS, Rybicki, BA, The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium & Batra, J 2016, 'Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation', Nature Communications, vol. 7, 10979, pp. 1-13. 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 - The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium

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

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

AN - SCOPUS:84963635486

SN - 2041-1723

VL - 7

SP - 1

EP - 13

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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