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

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Gusev , A , Shi , H , Kichaev , G , Pomerantz , M , Li , F , Long , H W , Ingles , S A , Kittles , R A , Strom , S S , Rybicki , B A , Nemesure , B , Isaacs , W B , Zheng , W , Pettaway , C A , Yeboah , E D , Tettey , Y , Biritwum , R B , Adjei , A A , Tay , E , Truelove , A , Niwa , S , Chokkalingam , A P , John , E M , Murphy , A B , Signorello , L B , Carpten , J , Leske , M C , Wu , S-Y , Hennis , A J M , Neslund-Dudas , C , Hsing , A W , Chu , L , Goodman , P J , Klein , E A , Witte , J S , Casey , G , Kaggwa , S , Cook , M B , Stram , D O , Blot , W J , Eeles , R A , Easton , D , Kote-Jarai , ZS , Al Olama , A A , Benlloch , S , Muir , K , Giles , G G , Southey , M C , Fitzgerald , L M , Taari , K & PRACTICAL Consortium 2016 , ' Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation ' Nature Communications , vol. 7 , 10979 . DOI: 10.1038/ncomms10979

Title: Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
Author: 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 G.; Southey, Melissa C.; Fitzgerald, Liesel M.; Taari, Kimmo; PRACTICAL Consortium
Contributor: University of Helsinki, Department of Surgery
Date: 2016-04
Language: eng
Number of pages: 13
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/161395
Abstract: 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.
Subject: GENOME-WIDE ASSOCIATION
SUSCEPTIBILITY LOCI
COMMON DISEASES
COMPLEX TRAITS
RISK
SNPS
ENHANCERS
ELEMENTS
PITFALLS
ENCODE
3122 Cancers
3126 Surgery, anesthesiology, intensive care, radiology
3111 Biomedicine
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