Open AccessIntegrative eQTL-Based Analyses Reveal the Biology of Breast Cancer Risk Loci
Author(s) -
Qiyuan Li,
Ji-Heui Seo,
Barbara E. Stranger,
Aaron McKenna,
Itsik Pe’er,
Thomas LaFramboise,
Myles Brown,
Svitlana Tyekucheva,
Matthew L. Freedman
Publication year - 2013
Publication title -
cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.304
H-Index - 776
eISSN - 1097-4172
pISSN - 0092-8674
DOI - 10.1016/j.cell.2012.12.034
Subject(s) - expression quantitative trait loci , biology , breast cancer , quantitative trait locus , genetics , dna methylation , locus (genetics) , gene , germline , genome wide association study , cpg site , human genetics , gene expression , computational biology , cancer , single nucleotide polymorphism , genotype
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.
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