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Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
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Muir, Kenneth and Lophatananon, Artitaya (2016) Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation. Nature Communications, 7 . 10979. doi:10.1038/ncomms10979 ISSN 2041-1723.
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Official URL: http://dx.doi.org/10.1038/ncomms10979
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.
Item Type: | Journal Article | ||||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | ||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||||
Library of Congress Subject Headings (LCSH): | Prostate -- Cancer -- Genetic aspects, Medical genetics -- Europe -- Africa, Genetic disorders | ||||||
Journal or Publication Title: | Nature Communications | ||||||
Publisher: | Nature Publishing Group | ||||||
ISSN: | 2041-1723 | ||||||
Official Date: | 7 April 2016 | ||||||
Dates: |
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Volume: | 7 | ||||||
Article Number: | 10979 | ||||||
DOI: | 10.1038/ncomms10979 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||
Date of first compliant deposit: | 18 May 2016 | ||||||
Date of first compliant Open Access: | 18 May 2016 | ||||||
Funder: | National Institutes of Health (U.S.) (NIH), Prostate Cancer Foundation, Wellcome Trust (London, England) | ||||||
Grant number: | F32 GM106584 R01 MH101244 R01 CA188392 U01 CA194393 R01 GM107427 R01 CA193910 (NIH), Prostate Cancer Foundation Challenge Award (PCF), 076113 |
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