Journal article
Deconvoluting complex tissues for expression quantitative trait locus-based analyses
Dana-Farber Cancer Institute1
Department of Systems Biology, Technical University of Denmark2
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark3
Massachusetts General Hospital/Harvard Medical School4
Broad Institute of Harvard University and Massachusetts Institute of Technology5
Breast cancer genome-wide association studies have pinpointed dozens of variants associated with breast cancer pathogenesis. The majority of risk variants, however, are located outside of known protein-coding regions. Therefore, identifying which genes the risk variants are acting through presents an important challenge.
Variants that are associated with mRNA transcript levels are referred to as expression quantitative trait loci (eQTLs). Many studies have demonstrated that eQTL-based strategies provide a direct way to connect a trait-associated locus with its candidate target gene. Performing eQTL-based analyses in human samples is complicated because of the heterogeneous nature of human tissue.
We addressed this issue by devising a method to computationally infer the fraction of cell types in normal human breast tissues. We then applied this method to 13 known breast cancer risk loci, which we hypothesized were eQTLs. For each risk locus, we took all known transcripts within a 2 Mb interval and performed an eQTL analysis in 100 reduction mammoplasty cases.
A total of 18 significant associations were discovered (eight in the epithelial compartment and 10 in the stromal compartment). This study highlights the ability to perform large-scale eQTL studies in heterogeneous tissues.
Language: | English |
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Publisher: | The Royal Society |
Year: | 2013 |
Pages: | 20120363-20120363 |
ISSN: | 14712970 and 09628436 |
Types: | Journal article |
DOI: | 10.1098/rstb.2012.0363 |
ORCIDs: | Eklund, Aron Charles |
Breast cancer risk Expression quantitative trait locus, Heterogeneous tissue SDG 3 - Good Health and Well-being Single nucleotide polymorphisms
Adipocytes Articles Breast Breast Neoplasms Computational Biology Epithelium Female Genetic Association Studies Genetic Heterogeneity Genetic Markers Humans Mammaplasty Predictive Value of Tests Quantitative Trait Loci Risk Factors Transcriptome breast cancer risk single nucleotide polymorphisms expression quantitative trait locus heterogeneous tissue