We investigated a third locus with a highly ranked HLC eGene that did not independently qualify as an eGene in the GTEx liver cohort, the FRK locus, although FRK qualified as an eGene in a cohort of ~1000 liver samples (Teslovich et al., 2010) (Figure 5A). In duplicate MPRA experiments, we profiled the regulatory activity of 76 variants linked (r2 ≥ 0.5) to the lead SNP at the locus (Table S9). The top MPRA SNP in the locus was rs10872142 (Figure 2C). In Europeans, rs10872142 is tightly linked to rs11153594 (r2 = 0.965), the lead SNP for LDL-C in the locus in the GLGC study, with each alternate allele copy of rs2131925 associated with a 0.9 mg/dL change in LDL-C (Teslovich et al., 2010). rs10872142 lies within intron 1 of FRK, whose protein product belongs to the TYR family of protein kinases. FRK was the only eGene at this locus in both the iPSC and HLC cohorts.
