Functional genomics and assays of regulatory activity detect mechanisms at loci for lipid traits and coronary artery disease.

Many genome-wide association studies (GWAS) have identified signals located in non-coding regions, and an increasing number of functional genomics annotations of regulatory elements and assays of regulatory activity have been used to investigate mechanisms. Genome-wide datasets that characterize chromatin structure help detect potential regulatory elements. Assays to experimentally assess candidate variants include transcriptional reporter assays, and recently, massively parallel reporter assays (MPRAs). Additionally, the effect of candidate regulatory elements and variants on gene expression and function can be evaluated using genomic editing with the CRISPR-Cas9 technology. We highlight some recent studies that employed these strategies to identify variant effects and elucidate molecular and/or biological mechanisms at GWAS loci for lipid traits and coronary artery disease.