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000153876 0247_ $$2doi$$a10.1002/gepi.22288
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000153876 0247_ $$2ISSN$$a0741-0395
000153876 0247_ $$2ISSN$$a1098-2272
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000153876 037__ $$aDKFZ-2020-00492
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000153876 1001_ $$aFeng, Helian$$b0
000153876 245__ $$aTranscriptome-wide association study of breast cancer risk by estrogen-receptor status.
000153876 260__ $$aNew York, NY$$bWiley-Liss$$c2020
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000153876 500__ $$a2020 Jul;44(5):442-468
000153876 520__ $$aPrevious 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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