One of the principal challenges of the post-GWAS era has been identifying functional variants and genes underlying complex disease susceptibility. In this work, we describe a methodological framework for functional pathway discovery that involves characterizing eQTL and ASE loci in population cohorts of iPSCs and iPSC-differentiated cells, high-throughput identification of candidate functional variants underlying eQTLs and ASE with MPRAs, and validation of prioritized variants in genome-edited cellular and mouse models. We focused our experimental efforts on interrogating lipid-associated eQTLs in HLCs and defining functional SNP-gene sets in three different eQTL loci.
