While eQTL studies have made valuable contributions to genetic research (e.g., [13]), there exist several practical limitations to consider. First, most eQTL studies are conducted in immortalized, lymphoblastoid cell lines (LCLs), which clearly have utility for the interpretation of human disease associations, particularly with immunity-related phenotypes [14], [15]. However, the use of such cell lines potentially introduces artifacts associated with immortalization, subsequent passage, and growth conditions prior to harvest [16]. Second, eQTLs may exhibit spatiotemporal specificity [17], [18], presumably driven by polymorphisms located within tissue specific regulatory elements, and eQTL studies may be maximally informative for any given trait when conducted in a relevant, non-transformed cell type. Third, environmental factors and other, mostly hidden, confounding variables are known to significantly affect gene expression levels and measurements [19]–[23]. Fourth, most eQTL studies fail to provide replication on an independent set of samples with independent experimental assessment (see [24]–[27], [23] for exceptions).
