Chunk #29 — RESULTS — Identifying functional genes associated with lipid metabolism via the HLC cohort

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

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We interrogated two other GLGC HLC eGenes, VKORC1 (locus associated with TG) and UBE2L3 (locus associated with HDL-C). Whereas VKORC1 independently qualified as a GTEx liver eGene (FDR < 5%), UBE2L3 did not. For VKORC1, we used a lipid-humanized mouse model to better reflect human triglyceride physiology (Burkhardt et al., 2010). Each of the two genes reproducibly altered the associated lipid trait (Figure 6A).