Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

ABCTB Investigators, HEBON Investigators, BCFR Investigators, OCGN Investigators, GEMO Study Collaborators, EMBRACE Collaborators, GC-HBOC Study Collaborators

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)442-468
Number of pages27
JournalGenetic Epidemiology
Issue number5
Publication statusPublished - Jul 2020


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