期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-018-06302-1
关键词
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资金
- NIH [R01-HG009120, R01-HG006399, U01-CA194393]
- European Commission's Seventh Framework Programme [223175 (HEALTH-F2-2009-223175)]
- Cancer Research UK [C5047/A7357, C1287/A16563, C5047/A3354, C5047/A10692, C16913/A6135, C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C8197/A16565]
- National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant [1U19 CA 148537-01]
- Institute of Cancer Research and The Everyman Campaign
- Prostate Cancer Research Foundation
- Prostate Action
- Orchid Cancer Appeal
- National Cancer Research Network UK
- National Cancer Research Institute (NCRI) UK
- NIHR
- National Health and Medical Research Council, Australia [126402, 209057, 251533, 396414, 450104, 504700, 504702, 504715, 623204, 940394, 614296]
- VicHealth
- Cancer Council Victoria
- Prostate Cancer Foundation of Australia
- Whitten Foundation
- Price Waterhouse Coopers
- Tattersall's
- US National Institutes of Health (NIH) [U19 CA 148537, X01HG007492, HHSN268201200008I]
- NIH NCI [U01 CA188392]
- European Community's Seventh Framework Programme [223175 (HEALTH-F2-2009-223175)]
- National Institutes of Health [CA128978]
- Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]
- Department of Defence [W81XWH-10-1-0341]
- Canadian Institutes of Health Research (CIHR)
- Komen Foundation for the Cure
- Breast Cancer Research Foundation
- Ovarian Cancer Research Fund
- US National Institutes of Health, National Cancer Institute [U01-CA98233, U01-CA98710, U01-CA98216, U01-CA98758]
- US National Institutes of Health, National Cancer Institute (Intramural Research Program of NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics)
- Swedish Cancer Foundation [09-0677, 11-484, 12-823]
- Cancer Risk Prediction Center (CRisP)
- Linneus Centre [70867902]
- Swedish Research Council
- Swedish Research Council [K2010-70X-20430-04-3, 2014-2269]
- Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health
- NIHR Biomedical Research Centre at the University of Cambridge
- Canadian Institutes of Health Research
- MRC [MR/N003284/1] Funding Source: UKRI
Although genome-wide association studies (GWAS) for prostate cancer (PrCa) have identified more than 100 risk regions, most of the risk genes at these regions remain largely unknown. Here we integrate the largest PrCa GWAS (N = 142,392) with gene expression measured in 45 tissues (N = 4458), including normal and tumor prostate, to perform a multi-tissue transcriptome-wide association study (TWAS) for PrCa. We identify 217 genes at 84 independent 1 Mb regions associated with PrCa risk, 9 of which are regions with no genome-wide significant SNP within 2 Mb. 23 genes are significant in TWAS only for alternative splicing models in prostate tumor thus supporting the hypothesis of splicing driving risk for continued oncogenesis. Finally, we use a Bayesian probabilistic approach to estimate credible sets of genes containing the causal gene at a pre-defined level; this reduced the list of 217 associations to 109 genes in the 90% credible set. Overall, our findings highlight the power of integrating expression with PrCa GWAS to identify novel risk loci and prioritize putative causal genes at known risk loci.
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