The spontaneously hypertensive rat (SHR) is a widely used rodent model of 
hypertension and metabolic syndrome. Previously we identified thousands of 
cis-regulated expression quantitative trait loci (eQTLs) across multiple tissues 
using a panel of rat recombinant inbred (RI) strains derived from Brown Norway 
and SHR progenitors. These cis-eQTLs represent potential susceptibility loci 
underlying physiological and pathophysiological traits manifested in SHR. We 
have prioritized 60 cis-eQTLs and confirmed differential expression between the 
parental strains by quantitative PCR in 43 (72%) of the eQTL transcripts. 
Quantitative trait transcript (QTT) analysis in the RI strains showed highly 
significant correlation between cis-eQTL transcript abundance and clinically 
relevant traits such as systolic blood pressure and blood glucose, with the 
physical location of a subset of the cis-eQTLs colocalizing with "physiological" 
QTLs (pQTLs) for these same traits. These colocalizing correlated cis-eQTLs 
(c3-eQTLs) are highly attractive as primary susceptibility loci for the 
colocalizing pQTLs. Furthermore, sequence analysis of the c3-eQTL genes 
identified single nucleotide polymorphisms (SNPs) that are predicted to affect 
transcription factor binding affinity, splicing and protein function. These 
SNPs, which potentially alter transcript abundance and stability, represent 
strong candidate factors underlying not just eQTL expression phenotypes, but 
also the correlated metabolic and physiological traits. In conclusion, by 
integration of genomic sequence, eQTL and QTT datasets we have identified 
several genes that are strong positional candidates for pathophysiological 
traits observed in the SHR strain. These findings provide a basis for the 
functional testing and ultimate elucidation of the molecular basis of these 
metabolic and cardiovascular phenotypes.