Mapping Baroreceptor Function to Genome: A Mathematical Modeling Approach

Abstract

To gain information about the genetic basis of a complex disease such as hypertension, blood pressure averages are often obtained and used as phenotypes in genetic mapping studies. In contrast, direct measurements of physiological regulatory mechanisms are not often obtained, due in large part to the time and expense required. As a result, little information about the genetic basis of physiological controlling mechanisms is available. Such information is important for disease diagnosis and treatment. In this article, we use a mathematical model of blood pressure to derive phenotypes related to the baroreceptor reflex, a short-term controller of blood pressure. The phenotypes are then used in a quantitative trait loci (QTL) mapping study to identify a potential genetic basis of this controller.

A Simple Regression-Based Method to Map Quantitative Trait Loci Underlying Function-Valued Phenotypes

“…A second approach is to fit parametric curves to the data from each individual and treat the parameter estimates as phenotypes in QTL analysis (e.g., see Kendziorski et al 2002). Ma et al (2002) expanded this approach by fitting a logistic growth model, g(t) = a 1+be −rt , at each putative QTL position, with parameters depending on QTL genotype.…”