Post-GWAS Analysis of Snip Data with Applications to Systolic Blood Pressure Sensitivity to Weight and Sodium Change

• Activity Number: 130
• Type: Contributed
• Date/Time: Monday, August 5, 2013 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Jie Liu*+ and Javier Cabrera and Jerry Q. Cheng and John Kostis
• Companies: Rutgers University and Dept of Statistics, Rutgers University and University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School and Robert Wood Johnson Medical School, Rutgers University
• Keywords: Clinical Trials ; Genotype ; Clustering algorithm ; Hypertension ; Sensitivity ; Greedy algorithm

Abstract

This work analyzes the Trial of Non-pharmacologic Interventions in the Elderly (TONE), which is a randomized observer blind clinical trial for elderly hypertensives on one or two medications. The patients received intervention in weight reduction, dietary sodium reduction, both weight and sodium reduction, or attention control. We examined the relationship of 21 gene polymorphisms previously found to be associated with hypertension, diabetes, or obesity, with the change in blood pressure. We used a recursive partitioning algorithm and a greedy search algorithm to select genotypes. To test for the difference in effects between the total data set and subgroups, we found the distribution of the difference of the estimates in question due to dependence, used to rank the different genotypes to decide their biological relevance. Greedy search provides a large quantity of possible genotypes. We gave a modified version of FDR treatment to multiplicity issue and performed PCA to merge similar highly ranked genotypes. We found that patients with certain genotypes treated with weight reduction or sodium reduction had significant different sensitivity from the overall population.