UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Identification of Novel Susceptibility Loci and Genes for Prostate Cancer Risk: A Transcriptome-Wide Association Study in over 140,000 European Descendants

Wu, L; Wang, J; Cai, Q; Cavazos, TB; Emami, NC; Long, J; Shu, X-O; ... PRACTICAL, CRUK, BPC3, CAPS, PEGASUS Consortia; + view all (2019) Identification of Novel Susceptibility Loci and Genes for Prostate Cancer Risk: A Transcriptome-Wide Association Study in over 140,000 European Descendants. Cancer Research , 79 (13) pp. 3192-3204. 10.1158/0008-5472.CAN-18-3536. Green open access

[thumbnail of Wu et al -2019 -Tanscriptome-wide association for pca - Cancer Res.pdf]
Preview
Text
Wu et al -2019 -Tanscriptome-wide association for pca - Cancer Res.pdf - Published Version

Download (922kB) | Preview

Abstract

Genome-wide association study–identified prostate cancer risk variants explain only a relatively small fraction of its familial relative risk, and the genes responsible for many of these identified associations remain unknown. To discover novel prostate cancer genetic loci and possible causal genes at previously identified risk loci, we performed a transcriptome-wide association study in 79,194 cases and 61,112 controls of European ancestry. Using data from the Genotype-Tissue Expression Project, we established genetic models to predict gene expression across the transcriptome for both prostate models and cross-tissue models and evaluated model performance using two independent datasets. We identified significant associations for 137 genes at P < 2.61 × 10−6, a Bonferroni-corrected threshold, including nine genes that remained significant at P < 2.61 × 10−6 after adjusting for all known prostate cancer risk variants in nearby regions. Of the 128 remaining associated genes, 94 have not yet been reported as potential target genes at known loci. We silenced 14 genes and many showed a consistent effect on viability and colony-forming efficiency in three cell lines. Our study provides substantial new information to advance our understanding of prostate cancer genetics and biology. SIGNIFICANCE: This study identifies novel prostate cancer genetic loci and possible causal genes, advancing our understanding of the molecular mechanisms that drive prostate cancer.

Type: Article
Title: Identification of Novel Susceptibility Loci and Genes for Prostate Cancer Risk: A Transcriptome-Wide Association Study in over 140,000 European Descendants
Open access status: An open access version is available from UCL Discovery
DOI: 10.1158/0008-5472.CAN-18-3536
Publisher version: https://doi.org/10.1158/0008-5472.CAN-18-3536
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Applied Health Research
URI: https://discovery.ucl.ac.uk/id/eprint/10084341
Downloads since deposit
26Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item