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Post genome-wide association studies functional characterization of prostate cancer risk loci

BACKGROUND: Over the last decade, genome-wide association studies (GWAS) have discovered many risk associated single nucleotide polymorphisms (SNPs) of prostate cancer (PCa). However, the majority of the associated PCa SNPs, including those in linkage disequilibrium (LD) blocks, are generally not lo...

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Autores principales: Jiang, Junfeng, Cui, Weirong, Vongsangnak, Wanwipa, Hu, Guang, Shen, Bairong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042239/
https://www.ncbi.nlm.nih.gov/pubmed/24564736
http://dx.doi.org/10.1186/1471-2164-14-S8-S9
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author Jiang, Junfeng
Cui, Weirong
Vongsangnak, Wanwipa
Hu, Guang
Shen, Bairong
author_facet Jiang, Junfeng
Cui, Weirong
Vongsangnak, Wanwipa
Hu, Guang
Shen, Bairong
author_sort Jiang, Junfeng
collection PubMed
description BACKGROUND: Over the last decade, genome-wide association studies (GWAS) have discovered many risk associated single nucleotide polymorphisms (SNPs) of prostate cancer (PCa). However, the majority of the associated PCa SNPs, including those in linkage disequilibrium (LD) blocks, are generally not located in protein coding regions. The systematical investigation of the functional roles of these SNPs, especially the non-coding SNPs, becomes very necessary and helpful to the understanding of the molecular mechanism of PCa. RESULTS: In this work, we proposed a comprehensive framework at network level to integrate the SNP annotation, target gene assignment, gene ontology (GO) classification, pathway enrichment analysis and regulatory network reconstruction to illustrate the molecular functions of PCa associated SNPs. By LD expansion, we first identified 1828 LD SNPs using 49 reported GWAS SNPs as a start. We carefully annotated these 1828 LD SNPs via either UCSC known genes, UCSC regulation elements, or expression Quantitative Trait Loci (eQTL) data. As a result, we found 1154 SNPs were functionally annotated and obtained 205 unique PCa genes for further enrichment analysis. The enriched GO biological processes and pathways were found mainly related to regulation of cell death, apoptosis, cell proliferation, and metabolic process, which have been proved essential to cancer development. We constructed PCa genes specific transcription regulatory networks, finding several important genetic regulators for PCa, such as IGF-1/IGF-2 receptors, SP1, CREB1, and androgen receptor (AR). CONCLUSIONS: A comprehensive framework was proposed for integrative and systematic analysis of PCa SNPs, the analysis can provide essential information for the understanding of the regulatory function of GWAS SNPs in PCa, and will facilitate the discovery of novel candidate biomarkers for diagnosis and prognosis of PCa.
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spelling pubmed-40422392014-06-04 Post genome-wide association studies functional characterization of prostate cancer risk loci Jiang, Junfeng Cui, Weirong Vongsangnak, Wanwipa Hu, Guang Shen, Bairong BMC Genomics Research BACKGROUND: Over the last decade, genome-wide association studies (GWAS) have discovered many risk associated single nucleotide polymorphisms (SNPs) of prostate cancer (PCa). However, the majority of the associated PCa SNPs, including those in linkage disequilibrium (LD) blocks, are generally not located in protein coding regions. The systematical investigation of the functional roles of these SNPs, especially the non-coding SNPs, becomes very necessary and helpful to the understanding of the molecular mechanism of PCa. RESULTS: In this work, we proposed a comprehensive framework at network level to integrate the SNP annotation, target gene assignment, gene ontology (GO) classification, pathway enrichment analysis and regulatory network reconstruction to illustrate the molecular functions of PCa associated SNPs. By LD expansion, we first identified 1828 LD SNPs using 49 reported GWAS SNPs as a start. We carefully annotated these 1828 LD SNPs via either UCSC known genes, UCSC regulation elements, or expression Quantitative Trait Loci (eQTL) data. As a result, we found 1154 SNPs were functionally annotated and obtained 205 unique PCa genes for further enrichment analysis. The enriched GO biological processes and pathways were found mainly related to regulation of cell death, apoptosis, cell proliferation, and metabolic process, which have been proved essential to cancer development. We constructed PCa genes specific transcription regulatory networks, finding several important genetic regulators for PCa, such as IGF-1/IGF-2 receptors, SP1, CREB1, and androgen receptor (AR). CONCLUSIONS: A comprehensive framework was proposed for integrative and systematic analysis of PCa SNPs, the analysis can provide essential information for the understanding of the regulatory function of GWAS SNPs in PCa, and will facilitate the discovery of novel candidate biomarkers for diagnosis and prognosis of PCa. BioMed Central 2013-12-09 /pmc/articles/PMC4042239/ /pubmed/24564736 http://dx.doi.org/10.1186/1471-2164-14-S8-S9 Text en Copyright © 2013 Jiang et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Jiang, Junfeng
Cui, Weirong
Vongsangnak, Wanwipa
Hu, Guang
Shen, Bairong
Post genome-wide association studies functional characterization of prostate cancer risk loci
title Post genome-wide association studies functional characterization of prostate cancer risk loci
title_full Post genome-wide association studies functional characterization of prostate cancer risk loci
title_fullStr Post genome-wide association studies functional characterization of prostate cancer risk loci
title_full_unstemmed Post genome-wide association studies functional characterization of prostate cancer risk loci
title_short Post genome-wide association studies functional characterization of prostate cancer risk loci
title_sort post genome-wide association studies functional characterization of prostate cancer risk loci
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042239/
https://www.ncbi.nlm.nih.gov/pubmed/24564736
http://dx.doi.org/10.1186/1471-2164-14-S8-S9
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