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Expression Quantitative Trait loci (QTL) in tumor adjacent normal breast tissue and breast tumor tissue
We investigate 71 single nucleotide polymorphisms (SNPs) identified in meta-analytic studies of genome-wide association studies (GWAS) of breast cancer, the majority of which are located in intergenic or intronic regions. To explore regulatory impacts of these variants we conducted expression quanti...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289428/ https://www.ncbi.nlm.nih.gov/pubmed/28152060 http://dx.doi.org/10.1371/journal.pone.0170181 |
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author | Quiroz-Zárate, Alejandro Harshfield, Benjamin J. Hu, Rong Knoblauch, Nick Beck, Andrew H. Hankinson, Susan E. Carey, Vincent Tamimi, Rulla M. Hunter, David J. Quackenbush, John Hazra, Aditi |
author_facet | Quiroz-Zárate, Alejandro Harshfield, Benjamin J. Hu, Rong Knoblauch, Nick Beck, Andrew H. Hankinson, Susan E. Carey, Vincent Tamimi, Rulla M. Hunter, David J. Quackenbush, John Hazra, Aditi |
author_sort | Quiroz-Zárate, Alejandro |
collection | PubMed |
description | We investigate 71 single nucleotide polymorphisms (SNPs) identified in meta-analytic studies of genome-wide association studies (GWAS) of breast cancer, the majority of which are located in intergenic or intronic regions. To explore regulatory impacts of these variants we conducted expression quantitative loci (eQTL) analyses on tissue samples from 376 invasive postmenopausal breast cancer cases in the Nurses’ Health Study (NHS) diagnosed from 1990–2004. Expression analysis was conducted on all formalin-fixed paraffin-embedded (FFPE) tissue samples (and on 264 adjacent normal samples) using the Affymetrix Human Transcriptome Array. Significance and ranking of associations between tumor receptor status and expression variation was preserved between NHS FFPE and TCGA fresh-frozen sample sets (Spearman r = 0.85, p<10^-10 for 17 of the 21 Oncotype DX recurrence signature genes). At an FDR threshold of 10%, we identified 27 trans-eQTLs associated with expression variation in 217 distinct genes. SNP-gene associations can be explored using an open-source interactive browser distributed in a Bioconductor package. Using a new a procedure for testing hypotheses relating SNP content to expression patterns in gene sets, defined as molecular function pathways, we find that loci on 6q14 and 6q25 affect various gene sets and molecular pathways (FDR < 10%). Although the ultimate biological interpretation of the GWAS-identified variants remains to be uncovered, this study validates the utility of expression analysis of this FFPE expression set for more detailed integrative analyses. |
format | Online Article Text |
id | pubmed-5289428 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-52894282017-02-17 Expression Quantitative Trait loci (QTL) in tumor adjacent normal breast tissue and breast tumor tissue Quiroz-Zárate, Alejandro Harshfield, Benjamin J. Hu, Rong Knoblauch, Nick Beck, Andrew H. Hankinson, Susan E. Carey, Vincent Tamimi, Rulla M. Hunter, David J. Quackenbush, John Hazra, Aditi PLoS One Research Article We investigate 71 single nucleotide polymorphisms (SNPs) identified in meta-analytic studies of genome-wide association studies (GWAS) of breast cancer, the majority of which are located in intergenic or intronic regions. To explore regulatory impacts of these variants we conducted expression quantitative loci (eQTL) analyses on tissue samples from 376 invasive postmenopausal breast cancer cases in the Nurses’ Health Study (NHS) diagnosed from 1990–2004. Expression analysis was conducted on all formalin-fixed paraffin-embedded (FFPE) tissue samples (and on 264 adjacent normal samples) using the Affymetrix Human Transcriptome Array. Significance and ranking of associations between tumor receptor status and expression variation was preserved between NHS FFPE and TCGA fresh-frozen sample sets (Spearman r = 0.85, p<10^-10 for 17 of the 21 Oncotype DX recurrence signature genes). At an FDR threshold of 10%, we identified 27 trans-eQTLs associated with expression variation in 217 distinct genes. SNP-gene associations can be explored using an open-source interactive browser distributed in a Bioconductor package. Using a new a procedure for testing hypotheses relating SNP content to expression patterns in gene sets, defined as molecular function pathways, we find that loci on 6q14 and 6q25 affect various gene sets and molecular pathways (FDR < 10%). Although the ultimate biological interpretation of the GWAS-identified variants remains to be uncovered, this study validates the utility of expression analysis of this FFPE expression set for more detailed integrative analyses. Public Library of Science 2017-02-02 /pmc/articles/PMC5289428/ /pubmed/28152060 http://dx.doi.org/10.1371/journal.pone.0170181 Text en © 2017 Quiroz-Zárate et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Quiroz-Zárate, Alejandro Harshfield, Benjamin J. Hu, Rong Knoblauch, Nick Beck, Andrew H. Hankinson, Susan E. Carey, Vincent Tamimi, Rulla M. Hunter, David J. Quackenbush, John Hazra, Aditi Expression Quantitative Trait loci (QTL) in tumor adjacent normal breast tissue and breast tumor tissue |
title | Expression Quantitative Trait loci (QTL) in tumor adjacent normal breast tissue and breast tumor tissue |
title_full | Expression Quantitative Trait loci (QTL) in tumor adjacent normal breast tissue and breast tumor tissue |
title_fullStr | Expression Quantitative Trait loci (QTL) in tumor adjacent normal breast tissue and breast tumor tissue |
title_full_unstemmed | Expression Quantitative Trait loci (QTL) in tumor adjacent normal breast tissue and breast tumor tissue |
title_short | Expression Quantitative Trait loci (QTL) in tumor adjacent normal breast tissue and breast tumor tissue |
title_sort | expression quantitative trait loci (qtl) in tumor adjacent normal breast tissue and breast tumor tissue |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289428/ https://www.ncbi.nlm.nih.gov/pubmed/28152060 http://dx.doi.org/10.1371/journal.pone.0170181 |
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