ArticlePloS one2017
Expression Quantitative Trait loci (QTL) in tumor adjacent normal breast tissue and breast tumor tissue.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Article
- Functional annotation of breast cancer risk loci: current progress and future directions.British journal of cancer · 2022Review
- MOSTWAS: Multi-Omic Strategies for Transcriptome-Wide Association Studies.PLoS genetics · 2021Article
- Characterization of SynonymousFrontiers in oncology · 2021Article
- Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes.Nature genetics · 2020Article
- Genetic associations of breast and prostate cancer are enriched for regulatory elements identified in disease-related tissues.Human genetics · 2019Article
- Cancer expression quantitative trait loci (eQTLs) can be determined from heterogeneous tumor gene expression data by modeling variation in tumor purity.Genome biology · 2018Article
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Authors and funding
11 authors.
Funding
Abstract
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.
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