Approaches to the Analysis of Complex Quantitative Phenotypes and Marker Map Construction Based on the Analysis of Rat Models of Hypertension

Essential hypertension is among the best examples of inherited complex quantitative phenotypes. Although this syndrome is well characterized for multiple pathophysiological circuits that have led to the development of potent pharmacological agents influencing blood pressure (BP), it remains a major health issue in Westernized populations because of its high prevalence and the increased risk of end-organ complications, including stroke, coronary heart disease, heart failure, peripheral vascular disease, and renal failure. Both genetic factors and “environmentalrd” factors such as diet, alcohol intake, and obesity are involved in the development of hypertension and its complications and contribute to its phenotypic heterogeneity. Investigating the genetic basis of BP control represents a paradigm to analyze gene-gene and gene-environment interactions. Although BP shows a continuous distribution in both human populations and experimental models, hypertension is arbitrarily defined by values above 140 mm Hg systolic and 90 mm Hg diastolic pressure. The utilization of quantitative values of the trait for statistical analysis of data derived from genetic studies represents a key strategy to overcome the arbitrary classification of hypertensive and normotensive individuals. This approach takes into account extreme values of the phenotypes, as well as quantitative values of the traits for a priori unaffected or undiagnosed individuals.