Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/157080
Title: Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants.
Author: Dadaev, Tokhir
Saunders, Edward J.
Mengual Brichs, Lourdes
PRACTICAL Consortium
Keywords: Càncer de pròstata
Càncer
Genètica humana
Prostate cancer
Cancer
Human genetics
Issue Date: 11-Jun-2018
Publisher: Nature Publishing Group
Abstract: Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
Note: Reproducció del document publicat a: https://doi.org/10.1038/s41467-018-04109-8
It is part of: Nature Communications, 2018, vol. 9, num. 1, p. 2256
URI: http://hdl.handle.net/2445/157080
Related resource: https://doi.org/10.1038/s41467-018-04109-8
ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Biomedicina)

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