Grant: Operating Grant

Hypertension (HT) is a well recognised global disease burden, which has yet to be resolved. Genomic determinants contribute significantly to HT and cardiovascular outcomes, which tend to cluster in families; however, their impact is blurred with age and progressive exposure to environmental factors. That is probably one of the reasons for only moderate success in determination of common genomic variants causative for HT in spite of significant endeavours in genomic analysis of hypertension. The so far identified variants contribute only modestly to overall risk. While genomic determinants are not modifiable, the degree of DNA methylation (epigenomics), resulting in modification of transcription of specific genes, and the telomeric length, are modifiable, reflecting past and current impacts of environmental factors. We hypothesize that integrating the information from genomic signatures of HT with progressively modifiable parameters will enhance our capacity to predict and prevent cardiovascular outcomes. To achieve this we will: a) analyze outcomes, temporal characteristics and familial clustering using hospital and genealogical records; b) partition hypertension into clinically and genetically defined subsets along phenotypic and genomic characteristics; c) search for genomic signatures of early nonfatal and fatal cardiovascular outcomes utilizing enhanced level of combined genomic and epigenomic analyses in defined subsets of hypertensive families d) use results of the above to develop "Personal Risk Prediction" tools in collaboration with our bioinformatics co-investigators and in partnership with IBM Research. The goal of our research is to develop predictive medicine tools to help doctors diagnose risks before they manifest, with a potential of primary prevention to reduce diseases burden.