Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes.

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Juliet D and Edwards, Stacey L and Antoniou, Antonis C and Chenevix-Trench, Georgia and Simard, Jacques and Easton, Douglas F and Kraft, Peter and Dunning, Alison M (2020) Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes. Nature genetics, 52 (1). pp. 56-73. ISSN 1546-1718

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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.

Item Type: Article
Impact Factor Value: 41.437
Subjects: Medical and Health Sciences > Basic medicine
Medical and Health Sciences > Clinical medicine
Divisions: Faculty of Medical Science
Depositing User: Katerina Kubelka-Sabit
Date Deposited: 13 Jan 2023 11:10
Last Modified: 13 Jan 2023 11:10

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