title: Integrative eQTL-based analyses reveal the biology of breast cancer risk loci.
abstract: Germline determinants of gene expression in tumors are infrequently studied due to the complexity of transcript regulation caused by somatically acquired alterations. We performed expression quantitative trait locus (eQTL)-based analyses using the multi-level information provided in The Cancer Genome Atlas (TCGA). Of the factors we measured, cis-acting eQTLs accounted for 1.2% of the total variation of tumor gene expression, while somatic copy-number alteration and CpG methylation accounted for 7.3% and 3.3%, respectively. eQTL analyses of 15 previously reported breast cancer risk loci resulted in the discovery of three variants that are significantly associated with transcript levels (false discovery rate [FDR] < 0.1). Our trans-based analysis identified an additional three risk loci to act through ESR1, MYC, and KLF4. These findings provide a more comprehensive picture of gene expression determinants in breast cancer as well as insights into the underlying biology of breast cancer risk loci.
authors: Department of Medical Oncology, The Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
authors: Qiyuan
authors: Q
authors: Li
authors: Ji-Heui
authors: JH
authors: Seo
authors: Barbara
authors: B
authors: Stranger
authors: Aaron
authors: A
authors: McKenna
authors: Itsik
authors: I
authors: Pe'er
authors: Thomas
authors: T
authors: Laframboise
authors: Myles
authors: M
authors: Brown
authors: Svitlana
authors: S
authors: Tyekucheva
authors: Matthew L
authors: ML
authors: Freedman
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D000090062:Kruppel-Like Factor 4; D040641:Quantitative Trait Loci
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