Genome-wide searches for blood pressure quantitative trait loci in the stroke-prone spontaneously hypertensive rat of a Japanese colony

Although several quantitative trait loci for blood pressure have been reported in stroke-prone spontaneously hypertensive rats (SHRSP), the results are not always concordant among different crosses. To evaluate potential confounding factors in linkage analysis, we performed genome-wide screens in F2 populations derived from SHRSP and Wistar-Kyoto rats of a Japanese colony.Two F cohorts were independently produced: F2-1 (110 male and 110 female rats), and F2-2 (174 male and 184 female rats). Blood pressure was measured longitudinally (from 2 to 5 months of age and 1 month after salt-loading) in F2-1, while it was measured at 13 weeks of age in F2-2. Subsequent to an initial screen with 251 markers in F2-1 male progeny, 170 markers were selected and characterized in the remaining populations.When 578 rats were analyzed together, markers from five chromosomal regions showed significant linkage to blood pressure at 13 weeks of age. The strongest and the most consistent linkage was found on rat chromosome 1 (a maximal log of the odds score reached 8.3). In the other regions, the degree of linkage was more prominent in either of sexes. Some evidence of age-specific and sex-specific linkage was detected in five additional regions in the F2-1 cohort. In the Japanese colony, however, there was no significant linkage to several chromosomal regions previously reported in other SHRSP colonies.Our data provide solid evidence of a chromosome-1 linkage and demonstrate the importance of aging, sex, and dietary manipulation in linkage analysis. Also, the combination of parental rat strains seems to be critical when searching for blood pressure quantitative trait loci.