Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

作者：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

来源：Nature Communications, 2016, 7(1): 10979.

DOI：10.1038/ncomms10979

Although genome-wide association studies have identified over 100 risk loci that explain similar to 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.

• 出版日期2016-4
• 单位河北医科大学; 西北大学