The specific objectives of this project are: 1) Identify genes with DAEs associated with breast cancer risk. We have already started phase I of a GWAS using DAE as a quantitative phenotype (preliminary data). In this proposal, we will perform the second phase of the GWAS through target RNA-seq in normal tissue of 50 patients with BC and 50 controls, of the most promising genes in phase I, followed by case-control association studies. 2) Map the cis-regulatory variants (rSNPs) for the identified risk genes. DAE analysis detects the cis-regulation target gene but not on the rSNP location. We have experience in successfully mapping cis-regulatory variants by correlating DAE information with genotype/haplotype data. 3) Characterise the new risk variants functionally. To characterise the underlying cis-regulation mechanism, in-silico, in vitro and in-vivo analyses of the best candidate genes will be performed in human breast cell lines and fresh tissue.