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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 publication

DOI

10.1038/ncomms10979

Type

Journal article

Journal

Nature communications

Publication Date

07/04/2016

Volume

7

Pages

10979 - 10979

Addresses

Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.

Keywords

PRACTICAL consortium, Cell Line, Tumor, Humans, Prostatic Neoplasms, Genetic Predisposition to Disease, Histones, Epigenesis, Genetic, Acetylation, Inheritance Patterns, Linkage Disequilibrium, Polymorphism, Single Nucleotide, African Americans, European Continental Ancestry Group, Male, Atlases as Topic, Genome-Wide Association Study, Genetic Loci