Understanding regional genomic variation associated with risk and etiology of chronic aging diseases

Searching for explanations of common non-infectious diseases via single-nucleotide polymorphisms (SNPs) in the human genome that are common (i.e., present in ≥ 5% of chromosomes in a population of interest), or not rare (≥ 1%), is an active area of genetic research that is characterized by simple yet fertile open problems that are often easy to formulate, but a challenge to solve. Our umbrella project began with genotype-phenotype studies of a cohort from Medellín, Colombia, and was driven by our interest in improving our understanding of genetic causes of the related phenotypes of cardiovascular disease, type 2 diabetes and cardiometabolic syndrome. The most recent of 3 grants awarded to us by Colciencias (2013-2017) focused on chronic diseases that preferentially affect higher age groups, and allowed us to develop special ways of analyzing, interpreting and integrating genetic data from loci that are associated with disease traits. In the four years of the current project (2017-2020) we use these together with other methods to deepen our understanding of key ‘pleiotropic’ (multiple-effect) loci such as 9p21.3 and 12q24 and other trait-associated loci that have been well characterized at the molecular (e.g., gene regulation) level. We search for molecular-level causality within these loci, a problem that can often not be effectively tackled using only classical strategies such as distance-based fine mapping and SNP-by-SNP association-strength comparisons. We are also deepening our search into causes, physical and genetic, of heart and cardiovascular system ailments, including risk factors such as hypertension and symptoms of major health importance such as arrhythmias.

Chronic diseases, disease trait-associated loci, genome and locus-wide association studies, genotyping, common SNPs, cardiovascular disease, aging diseases, molecular epidemiology, world population diversity, local data, haplotype analysis, molecular biology, gene regulation, genetic and physical causes of heart arrythmias