We focused first on the locus of CPNE1 (Figure 3A), an HLC eGene that did not independently qualify as an eGene in the GTEx liver cohort (i.e., did not have any associated SNPs with FDR < 5%), although it qualified as an eGene in a cohort of ~1000 liver samples (Teslovich et al., 2010). To identify candidate functional variants among all the SNPs in LD within the CPNE1 locus in an unbiased fashion, we performed MPRA experiments to rapidly profile the regulatory activity of 239 variants linked (r2 ≥ 0.5) to the lead SNP at the locus. Duplicate MPRAs were performed, and we rank-ordered SNPs by magnitude of allele-specific regulatory activity as measured by reporter expression (Table S9). The top MPRA SNP in the locus was rs2277862 (Figure 2C). Of note, rs2277862 was also the lead SNP for TC in the locus in the GLGC study, with each alternate allele copy associated with a 1.19 mg/dL change in TC (Teslovich et al., 2010).
