Association analysis identifies 65 new breast cancer risk loci

Research output: Contribution to journalArticle

Abstract

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

Details

Authors
Organisations
External organisations
  • University of Cambridge
  • Cyprus Institute of Neurology and Genetics
  • University of Washington
  • Harvard University
  • QIMR Berghofer Medical Research Institute
  • University of Toronto
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Cancer and Oncology

Keywords

  • ancestry, cancer, gene, genetic variation, genome, health risk, heritability, polymorphism, tumor, Europe, Far East
Original languageEnglish
Pages (from-to)92-94
Number of pages3
JournalNature
Volume551
Issue number7678
Publication statusPublished - 2017
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

Export Date: 20 November 2017