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Large-scale transcr...
Large-scale transcriptome-wide association study identifies new prostate cancer risk regions
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- Mancuso, Nicholas (author)
- Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
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- Gayther, Simon (author)
- Cedars Sinai Med Ctr, Ctr Bioinformat & Funct Genom, Los Angeles, CA 90048 USA.
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- Gusev, Alexander (author)
- Dana Farber Canc Inst, Boston, MA 02215 USA.
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- Zheng, Wei (author)
- Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med,Div Epidemiol, Nashville, TN 37232 USA.
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- Penney, Kathryn L. (author)
- Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
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- Kote-Jarai, Zsofia (author)
- Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England.;Royal Marsden NHS Fdn Trust, London SW3 6JJ, England.
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- Eeles, Rosalind (author)
- Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England.;Royal Marsden NHS Fdn Trust, London SW3 6JJ, England.
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- Freedman, Matthew (author)
- Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.;Harvard Med Sch, Boston, MA 02215 USA.
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- Haiman, Christopher (author)
- Univ Southern Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90015 USA.
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- Pasaniuc, Bogdan (author)
- Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.;Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.;Univ Calif Los Angeles, Bioinformat Interdept Program, Los Angeles, CA 90095 USA.
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Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA Cedars Sinai Med Ctr, Ctr Bioinformat & Funct Genom, Los Angeles, CA 90048 USA. (creator_code:org_t)
- 2018-10-04
- 2018
- English.
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Mancuso, Nichola ...
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Gayther, Simon
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Gusev, Alexander
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Zheng, Wei
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Penney, Kathryn ...
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Kote-Jarai, Zsof ...
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show more...
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Eeles, Rosalind
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Freedman, Matthe ...
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Haiman, Christop ...
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Pasaniuc, Bogdan
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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Nature Communica ...
- By the university
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Uppsala University