TY - JOUR
T1 - Integrative eQTL-based analyses reveal the biology of breast cancer risk loci
AU - Li, Qiyuan
AU - Seo, Ji Heui
AU - Stranger, Barbara Elaine
AU - McKenna, Aaron
AU - Pe'Er, Itsik
AU - Laframboise, Thomas
AU - Brown, Myles
AU - Tyekucheva, Svitlana
AU - Freedman, Matthew L.
N1 - Funding Information:
We thank Dr. Giovanni Parmigiani for his suggestions with respect to the statistical modeling. We thank Dr. Gad Getz for suggestions on data processing. M.L.F. is a Howard Hughes Medical Institute Physician-Scientist Early Career Awardee ( www.hhmi.org ) and a recipient of a 2009 Claudia Adams Barr award ( www.dana-farber.org ). This work was supported by grants from the U.S. National Institutes of Health (NIH) (ELLIPSE/GAME-ON-U19 CA148537 to M.L.F. and R01 CA131341 to T.L. and I.P.), the Mayer Foundation (to M.L.F.), the H.L. Snyder Medical Foundation (to M.L.F.), the Kohlberg Foundation, and the A. David Mazzone Awards Program (to M.L.F.).
PY - 2013/1/31
Y1 - 2013/1/31
N2 - 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.
AB - 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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U2 - 10.1016/j.cell.2012.12.034
DO - 10.1016/j.cell.2012.12.034
M3 - Article
C2 - 23374354
AN - SCOPUS:84873288058
SN - 0092-8674
VL - 152
SP - 633
EP - 641
JO - Cell
JF - Cell
IS - 3
ER -
