In order to assess whether the eQTL/ASE analyses could identify new functional variants and genes at GWAS loci, we chose to focus on blood lipid traits [total cholesterol (TC), LDL-C, HDL-C, and triglyceride (TG) levels] because of the major influence of the liver on these traits, as well as the ability to interrogate the functional effects of candidate genes on blood lipid levels in mice. To identify potential functional variants and genes in the HLC, iPSC, and GTEx liver cohorts, we interrogated 7,240 SNPs across 157 loci associated with one or more of the four lipid traits (P < 5 × 10−8) from the Global Lipids Genetics Consortium (GLGC) (Global Lipids Genetics Consortium, 2013) for association with the expression of any gene within 1 Mb (eQTL FDR < 5%). Across the 157 loci, there were 32 eGenes in the HLCs, 43 eGenes in the iPSCs, and 30 eGenes in the GTEx livers (Figure 2A, Table S7). In the HLCs, 205 genes at the GLGC loci exhibited significant ASE (FDR < 5%) in at least one individual, potentially identifying additional candidate functional genes that were missed by the eQTL analyses.
