NBCS Collaborators, ABCTB Investigators and ConFab/AOCS Investigators (2017) Association analysis identifies 65 new breast cancer risk loci. Nature, 551. pp. 92-94. ISSN 0028-0836
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 ancestry1. 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Macmillan Publishers Limited, part of Springer Nature. This is an author produced version of a paper subsequently published in Nature. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number CANCER RESEARCH UK (CRUK) C9267/A25152 BREAST CANCER NOW TB2017SHEF |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 20 Oct 2017 12:30 |
Last Modified: | 07 Sep 2018 16:47 |
Published Version: | https://doi.org/10.1038/nature24284 |
Status: | Published |
Publisher: | Nature Publishing Group |
Refereed: | Yes |
Identification Number: | 10.1038/nature24284 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:122685 |