Large, Diverse Population Cohorts of hiPSCs and Derived Hepatocyte-like Cells Reveal Functional Genetic Variation at Blood Lipid-Associated Loci. Large, Diverse Population Cohorts of hiPSCs and Derived Hepatocyte-like Cells Reveal Functional Genetic Variation at Blood Lipid-Associated Loci

Musunuru, Brown, Rader, and colleagues of the NHLBI NextGen consortium use multi-ethnic population cohorts of iPSCs and differentiated hepatocyte-like cells, in combination with mouse models, to discover and validate functional DNA variants and genes at blood lipid- associated loci previously identified by genome-wide association studies. Overall design: Peripheral blood mononuclear cells (PBMCs) isolated 91 individuals (43% African Americans and 55% European Americans; 60% women and 40% men) were used to generate iPSCs. PBMCs were differentiated into HLCs which were morphologically similar to primary hepatocytes. RNA-seq data was generated from iPSCs (n=89), HLCs (n=86), primary hepatocytes (n=4) and whole liver in GTEx cohort (n=96). The majority of data for this study is deposited in at dbGaP for controlled access: https://www.ncbi.nlm.nih.gov/gap/?term=phs001341