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

Helian Feng, Alexander Gusev, Bogdan Pasaniuc, GEMO Study Collaborators, Liene Nikitina-Zake (Member of the Working Group)

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)
1 Downloads (Pure)


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
Externally publishedYes


  • Breast Neoplasms/genetics
  • Estrogens/metabolism
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genomics
  • Humans
  • Receptors, Estrogen/metabolism
  • Risk Assessment
  • Transcriptome
  • Vesicular Transport Proteins/genetics

Field of Science*

  • 1.6 Biological sciences
  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database


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