Fachal, L, Aschard, H, Beesley, J et al. (338 more authors) (2020) Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes. Nature Genetics, 52 (1). pp. 56-73. ISSN 1061-4036
Abstract
Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Author(s). This is an author-produced version of a paper subsequently published in Nature Genetics. 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 Human Metabolism (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Oncology (Sheffield) |
Funding Information: | Funder Grant number CANCER RESEARCH UK C9267/A25152 BREAST CANCER NOW TB2O19BAR |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 17 Jan 2020 14:12 |
Last Modified: | 07 Jul 2020 00:38 |
Status: | Published |
Publisher: | Nature Research |
Refereed: | Yes |
Identification Number: | 10.1038/s41588-019-0537-1 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:155771 |