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024 7 _ |a 10.1002/gepi.22288
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024 7 _ |a pmid:32115800
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024 7 _ |a 0741-0395
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024 7 _ |a 1098-2272
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037 _ _ |a DKFZ-2020-00492
041 _ _ |a eng
082 _ _ |a 610
100 1 _ |a Feng, Helian
|b 0
245 _ _ |a Transcriptome-wide association study of breast cancer risk by estrogen-receptor status.
260 _ _ |a New York, NY
|c 2020
|b Wiley-Liss
336 7 _ |a article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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500 _ _ |a 2020 Jul;44(5):442-468
520 _ _ |a Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.
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