Journal article
Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
Alexander Gusev, Huwenbo Shi, Gleb Kichaev, Mark Pomerantz, Fugen Li, Henry W Long, Sue A Ingles, Rick A Kittles, Sara S Strom, Benjamin A Rybicki, Barbara Nemesure, William B Isaacs, Wei Zheng, Curtis A Pettaway, Edward D Yeboah, Yao Tettey, Richard B Biritwum, Andrew A Adjei, Evelyn Tay, Ann Truelove Show all
NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2016
DOI: 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 adenoc7ar..
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Grants
Awarded by NIH fellowship
Awarded by NIH
Awarded by Wellcome Trust
Awarded by European Commission's Seventh Framework Programme
Awarded by Cancer Research UK
Awarded by National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative Grant
Awarded by National Institutes of Health
Awarded by Post-Cancer GWAS initiative
Awarded by Department of Defense
Awarded by Linneus Centre
Awarded by Swedish Research Council
Awarded by Swedish Cancer Foundation
Awarded by US National Cancer Institute, National Institutes of Health
Awarded by US National Cancer Institute
Awarded by National Health and Medical Research Council, Australia
Awarded by Bulgarian National Science Fund, Ministry of Education and Science
Awarded by NIHR Health Technology Assessment Programme
Awarded by Medical Research Council of England
Awarded by US Dept of Defense award
Awarded by Australia Project Grant
Awarded by Vanderbilt-Ingram Cancer Center
Awarded by Competitive Research Funding of the Tampere University Hospital
Awarded by National Cancer Institute
Awarded by Medical Research Council
Awarded by National Institute for Health Research
Awarded by The Francis Crick Institute
Awarded by Cancer Foundation Finland sr
Awarded by NATIONAL CANCER INSTITUTE
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
Awarded by NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
Awarded by NATIONAL INSTITUTE OF MENTAL HEALTH
Funding Acknowledgements
This work was supported by NIH fellowship F32 GM106584 (AG), NIH grants R01 MH101244(A.G.), R01 CA188392 (B.P.), U01 CA194393(B.P.), R01 GM107427 (M.L.F.), R01 CA193910 (M.L.F./M.P.) and Prostate Cancer Foundation Challenge Award (M.L.F./M.P.). This study makes use of data generated by the Wellcome Trust Case Control Consortium and the Wellcome Trust Sanger Institute. A full list of the investigators who contributed to the generation of the Wellcome Trust Case Control Consortium data is available on www.wtccc.org.uk. Funding for the Wellcome Trust Case Control Consortium project was provided by the Wellcome Trust under award 076113. This study makes use of data generated by the UK10K Consortium. A full list of the investigators who contributed to the generation of the data is available online (http://www.UK10K.org). The PRACTICAL consortium was supported by the following grants: European Commission's Seventh Framework Programme grant agreement no 223175 (HEALTH-F2-2009-223175), Cancer Research UK Grants C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, C16913/A6135 and The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative Grant: no. 1 U19 CA 148537-01 (the GAME-ON initiative); Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007 and C5047/A10692), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112-the GAME-ON initiative), the Department of Defense (W81XWH-10-1-0341), A Linneus Centre (Contract ID 70867902), Swedish Research Council (grant no K2010-70X-20430-04-3), the Swedish Cancer Foundation (grant no 09-0677), grants RO1CA056678, RO1CA082664 and RO1CA092579 from the US National Cancer Institute, National Institutes of Health; US National Cancer Institute (R01CA72818); support from The National Health and Medical Research Council, Australia (126402, 209057, 251533, 396414, 450104, 504700, 504702, 504715, 623204, 940394 and 614296); NIH grants CA63464, CA54281 and CA098758; US National Cancer Institute (R01CA128813, PI: J.Y. Park); Bulgarian National Science Fund, Ministry of Education and Science (contract DOO-119/2009; DUNK01/2-2009; DFNI-B01/28/2012); Cancer Research UK grants [C8197/A10123] and [C8197/A10865]; grant code G0500966/75466; NIHR Health Technology Assessment Programme (projects 96/20/06 and 96/20/99); Cancer Research UK grant number C522/A8649, Medical Research Council of England grant number G0500966, ID 75466 and The NCRI, UK; The US Dept of Defense award W81XWH-04-1-0280; Australia Project Grant [390130, 1009458] and Enabling Grant [614296 to APCB]; the Prostate Cancer Foundation of Australia (Project Grant [PG7] and Research infrastructure grant [to APCB]); NIH grant R01 CA092447; Vanderbilt-Ingram Cancer Center (P30 CA68485); Cancer Research UK [C490/A10124] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge; Competitive Research Funding of the Tampere University Hospital (9N069 and X51003); Award Number P30CA042014 from the National Cancer Institute.