Abstract 88: Systems Biology Approaches to Exploring Molecular Mechanisms Underlying Blood Pressure Regulation

Blood pressure (BP) is a complex trait that is influenced by both genetic and environment factors. Recent genome-wide association studies (GWAS) have identified about 30 genetic loci that are associated with systolic and diastolic blood pressure (SBP, DBP) and hypertension. However, the molecular mechanisms underlying the GWAS associations remain unclear. We hypothesize that BP-associated genetic variants with both strong and subtle effects drive shifts in gene subnetworks that in turn affect BP. We surveyed BP-associated molecular interactions in Framingham offspring cohort participants (n=2461; 55% women; age range 40-92 yrs.) by integrating gene expression profiles, expression-associated SNPs (eSNPs), and BP GWAS with network approaches. Peripheral whole blood samples were collected and large-scale transcriptomic microarray analysis was performed on all available participants who attended a clinic visit in 2005-2008. Based on pedigrees the samples were split into a discovery set (n=1421) and a replication set (n=820). The expression levels of 661 genes (FDR