Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes.
Accepted version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
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.
Description
Keywords
Journal Title
Conference Name
Journal ISSN
1546-1718
Volume Title
Publisher
Publisher DOI
Sponsorship
European Commission Horizon 2020 (H2020) Societal Challenges (634935)
European Commission Horizon 2020 (H2020) Societal Challenges (633784)
European Commission (223175)
National Cancer Institute (U19CA148065)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (656144)
Cancer Research UK (10710)
Cancer Research UK (16563)
Cancer Research UK (10118)
Wellcome Trust (203477/Z/16/Z)
Cancer Research UK (20861)
Cancer Research UK (23382)
Cancer Research UK (16565)
Cancer Research UK (20411)