Finally, to assess whether the HLC cohort could be used to discover lipid-functional genes that were not directly nominated by the GLGC HLC eGene analysis, we interrogated ACAA2. ACAA2 was notable in that it was one of the top-ranked HLC-specific eGenes in the genome-wide iPSC/HLC meta-analysis (P = 4 × 10−13; Table S6) and exhibited HLC-specific differential ASE relative to iPSCs in the genome-wide ASE analysis (P = 2 × 10−4; Table S4). We found that expression of ACAA2 reproducibly altered blood HDL-C levels in mice (Figure 6A). Taken together, all of these findings establish that cohorts of iPSC-differentiated cells can discover new functional genes underlying complex traits.
