Gusev, A;
Shi, H;
Kichaev, G;
Pomerantz, M;
Li, F;
Long, HW;
Ingles, SA;
... Pasaniuc, B; + view all
(2016)
Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.
Nature Communications
, 7
, Article 10979. 10.1038/ncomms10979.
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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.
| Type: | Article |
|---|---|
| Title: | Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ncomms10979 |
| Publisher version: | http://dx.doi.org/10.1038/ncomms10979 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Biological sciences, Cancer, Genetics |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Applied Health Research |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1482905 |
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