Numerous problems plague many current statistical approaches to mapping genes influencing complex quantitative traits such as the level of blood pressure. It is important to develop better ways of assessing and measuring physiologic processes thought to underlie the pathogenesis of hypertension. These problems are not necessarily insurmountable, but will require the development of techniques that are much more flexible and appropriate than the majority of methods proposed to date. The goal of project 4 is to develop appropriate statistical and analytical techniques for the generation and analysis of data collected from the three applied projects associated with this SCOR proposal. Since hypertension is by nature a complex, multifactorial, and genetically heterogenous disorder, three related but specific issues will be the focus of this project: 1. justification of the data analytic techniques to be used for each type of data gathered (Milwaukee/Chicago African-American sibships; genetically isolated Chicoutimi sibships; Dahl F2 intercross rats); 2. develop new extensions of sib pair and affected pedigree methods for gene mapping (based on extracting the full information from multipoint linkage information of all markers in a region), characterize the statistical properties of these methods, and implement the methods in appropriate software; 3. development of novel time series and mathematical modeling- based approaches for the determination of novel hypertension associated phenotypes. We will address the extremely important issues concerning the proper assessment of hypertension associated phenotypes that characterize the dysfunctional or pathophysiological state of hypertension in order to provide the most comprehensive understanding of the genomic regions and specific genes which contribute to this disease.
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