Following the replication of 2 of 3 eQTLs in neuronal tissue, we sought to directly assess functionality of these SNPs in vitro through the use of luciferase reporter gene assays. We generated constructs with both alleles at each of the 3 SNPs, rs3933331, rs7858819, and rs301430, and used human neuroblastoma (SH-SY5Y) and rat pheochromocytoma (PC12) cell lines for transfection. As depicted in Figure 3, the 2 alleles at rs301430 had a highly significant differential effect on reporter gene expression in both cell lines (P<.001 for both). In line with the T allele–associated decrease in SLC1A1 expression in lymphoblastoid cell lines and neuronal tissue, the rs301430 construct with the T allele showed about 50% decreased expression compared with the C allele (Figure 3).
