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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Helian Feng
  • Alexander Gusev
  • Bogdan Pasaniuc
  • Lang Wu
  • Jirong Long
  • Zomoroda Abu-full
  • Kristiina Aittomäki
  • Irene L. Andrulis
  • Hoda Anton-Culver
  • Antonis C. Antoniou
  • Adalgeir Arason
  • Volker Arndt
  • Kristan J. Aronson
  • Banu K. Arun
  • Ella Asseryanis
  • Paul L. Auer
  • Jacopo Azzollini
  • Judith Balmaña
  • Rosa B. Barkardottir
  • Daniel R. Barnes
  • Daniel Barrowdale
  • Matthias W. Beckmann
  • Sabine Behrens
  • Javier Benitez
  • Marina Bermisheva
  • Katarzyna Białkowska
  • Ana Blanco
  • Carl Blomqvist
  • Bram Boeckx
  • Natalia V. Bogdanova
  • Bojesen, Stig Egil
  • Manjeet K. Bolla
  • Bernardo Bonanni
  • Ake Borg
  • Hiltrud Brauch
  • Hermann Brenner
  • Ignacio Briceno
  • Annegien Broeks
  • Thomas Brüning
  • Barbara Burwinkel
  • Qiuyin Cai
  • Trinidad Caldés
  • Maria A. Caligo
  • Ian Campbell
  • Sander Canisius
  • Hans Christiansen
  • Ejlertsen, Bent Laursen
  • Henrik Flyger
  • Nielsen, Finn Cilius
  • Qin Wang
  • ABCTB Investigators
  • HEBON Investigators
  • BCFR Investigators
  • OCGN Investigators
  • GEMO Study Collaborators
  • EMBRACE Collaborators
  • GC-HBOC Study Collaborators

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
JournalGenetic Epidemiology
Volume44
Issue number5
Pages (from-to)442-468
ISSN0741-0395
DOIs
Publication statusPublished - 2020

    Research areas

  • breast cancer subtype, causal gene, GWAS, TWAS

ID: 253400713