Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
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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; Southey, Melissa C; Fitzgerald, Liesel M; Nordestgaard, Børge G; PRACTICAL consortium.
In: Nature Communications, Vol. 7, 10979, 2016, p. 1-13.Research output: Contribution to journal › Journal article › Research › peer-review
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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
AU - Southey, Melissa C
AU - Fitzgerald, Liesel M
AU - Nordestgaard, Børge G
AU - PRACTICAL consortium
PY - 2016
Y1 - 2016
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.
KW - Acetylation
KW - African Americans
KW - Atlases as Topic
KW - Cell Line, Tumor
KW - Epigenesis, Genetic
KW - European Continental Ancestry Group
KW - Genetic Loci
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Histones
KW - Humans
KW - Inheritance Patterns
KW - Linkage Disequilibrium
KW - Male
KW - Polymorphism, Single Nucleotide
KW - Prostatic Neoplasms
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
KW - Research Support, U.S. Gov't, Non-P.H.S.
U2 - 10.1038/ncomms10979
DO - 10.1038/ncomms10979
M3 - Journal article
C2 - 27052111
VL - 7
SP - 1
EP - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 10979
ER -
ID: 177067908