CAUSEL: an epigenome- and genome-editing pipeline for establishing function of noncoding GWAS variants.

ABSTRACT: The vast majority of disease-associated single-nucleotide polymorphisms (SNPs) mapped by genome-wide association studies (GWASs) are located in the non-protein-coding genome, but establishing the functional and mechanistic roles of these sequence variants has proven challenging. Here we describe a general pipeline in which candidate functional SNPs are first evaluated by fine mapping, epigenomic profiling, and epigenome editing, and then interrogated for causal function by using genome editing to create isogenic cell lines followed by phenotypic characterization. To validate this approach, we analyzed the 6q22.1 prostate cancer risk locus and identified rs339331 as the top-scoring SNP. Epigenome editing confirmed that the rs339331 region possessed regulatory potential. By using transcripti

SUBMITTER: Spisak S 

PROVIDER: S-EPMC4746056 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature