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Top associated SNPs in prostate cancer are significantly enriched in cis-expression quantitative trait loci and at transcription factor binding sites

While genome-wide association studies (GWAS) have revealed thousands of disease risk single nucleotide polymorphisms (SNPs), their functions remain largely unknown. Recent studies have suggested the regulatory roles of GWAS risk variants in several common diseases; however, the complex regulatory st...

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Autores principales: Jiang, Junfeng, Jia, Peilin, Shen, Bairong, Zhao, Zhongming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171620/
https://www.ncbi.nlm.nih.gov/pubmed/25026280
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author Jiang, Junfeng
Jia, Peilin
Shen, Bairong
Zhao, Zhongming
author_facet Jiang, Junfeng
Jia, Peilin
Shen, Bairong
Zhao, Zhongming
author_sort Jiang, Junfeng
collection PubMed
description While genome-wide association studies (GWAS) have revealed thousands of disease risk single nucleotide polymorphisms (SNPs), their functions remain largely unknown. Recent studies have suggested the regulatory roles of GWAS risk variants in several common diseases; however, the complex regulatory structure in prostate cancer is unclear. We investigated the potential regulatory roles of risk variants in two prostate cancer GWAS datasets by their interactions with expression quantitative trait loci (eQTL) and/or transcription factor binding sites (TFBSs) in three populations. Our results indicated that the moderately associated GWAS SNPs were significantly enriched with cis-eQTLs and TFBSs in Caucasians (CEU), but not in African Americans (AA) or Japanese (JPT); this was also observed in an independent pan-cancer related SNPs from the GWAS Catalog. We found that the eQTL enrichment in the CEU population was tissue-specific to eQTLs from CEU lymphoblastoid cell lines. Importantly, we pinpointed two SNPs, rs2861405 and rs4766642, by overlapping results from cis-eQTL and TFBS as applied to the CEU data. These results suggested that prostate cancer associated SNPs and pan-cancer associated SNPs are likely to play regulatory roles in CEU. However, the negative enrichment results in AA or JPT and the potential mechanisms remain to be elucidated in additional samples.
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spelling pubmed-41716202014-09-23 Top associated SNPs in prostate cancer are significantly enriched in cis-expression quantitative trait loci and at transcription factor binding sites Jiang, Junfeng Jia, Peilin Shen, Bairong Zhao, Zhongming Oncotarget Research Paper While genome-wide association studies (GWAS) have revealed thousands of disease risk single nucleotide polymorphisms (SNPs), their functions remain largely unknown. Recent studies have suggested the regulatory roles of GWAS risk variants in several common diseases; however, the complex regulatory structure in prostate cancer is unclear. We investigated the potential regulatory roles of risk variants in two prostate cancer GWAS datasets by their interactions with expression quantitative trait loci (eQTL) and/or transcription factor binding sites (TFBSs) in three populations. Our results indicated that the moderately associated GWAS SNPs were significantly enriched with cis-eQTLs and TFBSs in Caucasians (CEU), but not in African Americans (AA) or Japanese (JPT); this was also observed in an independent pan-cancer related SNPs from the GWAS Catalog. We found that the eQTL enrichment in the CEU population was tissue-specific to eQTLs from CEU lymphoblastoid cell lines. Importantly, we pinpointed two SNPs, rs2861405 and rs4766642, by overlapping results from cis-eQTL and TFBS as applied to the CEU data. These results suggested that prostate cancer associated SNPs and pan-cancer associated SNPs are likely to play regulatory roles in CEU. However, the negative enrichment results in AA or JPT and the potential mechanisms remain to be elucidated in additional samples. Impact Journals LLC 2014-07-09 /pmc/articles/PMC4171620/ /pubmed/25026280 Text en Copyright: © 2014 Jiang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Jiang, Junfeng
Jia, Peilin
Shen, Bairong
Zhao, Zhongming
Top associated SNPs in prostate cancer are significantly enriched in cis-expression quantitative trait loci and at transcription factor binding sites
title Top associated SNPs in prostate cancer are significantly enriched in cis-expression quantitative trait loci and at transcription factor binding sites
title_full Top associated SNPs in prostate cancer are significantly enriched in cis-expression quantitative trait loci and at transcription factor binding sites
title_fullStr Top associated SNPs in prostate cancer are significantly enriched in cis-expression quantitative trait loci and at transcription factor binding sites
title_full_unstemmed Top associated SNPs in prostate cancer are significantly enriched in cis-expression quantitative trait loci and at transcription factor binding sites
title_short Top associated SNPs in prostate cancer are significantly enriched in cis-expression quantitative trait loci and at transcription factor binding sites
title_sort top associated snps in prostate cancer are significantly enriched in cis-expression quantitative trait loci and at transcription factor binding sites
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171620/
https://www.ncbi.nlm.nih.gov/pubmed/25026280
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