The second complementary study, ie, luciferase reporter gene constructs, was aimed at direct functional assessment of individual SNPs. While association analyses with tissue samples or cell lines have the advantage of more closely resembling in vivo conditions, the eQTLs do not necessarily have to directly confer functionality, as they may merely be in linkage disequilibrium with the actual functional polymorphism. We addressed this uncertainty by examining individual polymorphisms in vitro with reporter gene assays. Our luciferase data for rs301430 suggest that this variant is indeed directly functional. Additional studies are now needed to elucidate the molecular mechanisms through which rs301430 affects gene expression.
