We propose an alternative method to identify eQTLs that builds on traditional approaches. In contrast to genome-wide techniques, our method determines the significance of an association between an expression trait and a locus with respect to the set of all associations to the expression trait. The use of this specific information facilitates identification of expression traits that have an expression profile that is characterized by a single exceptional association to a locus.Our approach identifies expression traits that have exceptional associations regardless of the genome-wide significance of those associations. This property facilitates the identification of possible false negatives for genome-wide significance. Further, our approach has the property of prioritizing expression traits that are affected by few strong associations. Expression traits identified by this method may warrant additional study because their expression level may be affected by targeting genes near a single locus.We demonstrate our method by identifying eQTL hotspots in Plasmodium falciparum (malaria) and Saccharomyces cerevisiae (yeast). We demonstrate the prioritization of traits with few strong genetic effects through Gene Ontology (GO) analysis of Yeast. Our results are strongly consistent with results gathered using genome-wide methods and identify additional hotspots and eQTLs.New eQTLs and hotspots found with this method may represent regions of the genome or biological processes that are controlled through few relatively strong genetic interactions. These points of interest warrant experimental investigation.eQTL studies use gene expression data and genetic variation between individuals to calculate the association between expression traits and genotypes. In the context of eQTL studies an 'expression trait' refers to the quantity of labeled (c)DNA hybridizing to a single probe on a microarray. An eQTL is a strong association between one locus in the genome and one expression trait.