Breast cancer has a strong genetic risk component, and recently,
cis-regulatory single nucleotide polymorphisms (SNP) have been
associated with it. Current efforts are focused on the full
understanding of the cis-regulatory mechanisms involved.
Most studies functionally characterising GWAS loci for breast
cancer, have focused solely on the effect of regulatory SNPs
(rSNPs) on transcription factor binding at promoters and enhancers.
However, sequence changes can also have potential effects on, for
example, splicing, microRNA (miRNA) activity and epigenetic
regulation. Here we have initiated the study of genetic variants affecting
alternative splicing in breast cancer, by identifying splicing QTLs which are associated with risk.
We have used psichomics to quantify alternative splicing isoforms in normal breast RNA-seq data (phs000424.v8.p2 NHGRI GTEx), and mapped the sQTL using tensorQTL. Then we compared the list of significant sQTLs with breast cancer known risk variants, by using gwarapidd to retrieve data from the GWAS Catalog.
Results presented are preliminary.