American Heart Association Cardiovascular Genome-Phenome Study: foundational basis and program.

Abstract

The American Heart Association has established the Cardiovascular Genome-Phenome Study (CV-GPS) as a means by which to achieve the goal of using modern genomics and phenotyping optimally to combat cardiovascular disease (CVD). CVD remains the leading cause of death in the United States and has become a major cause of morbidity and mortality worldwide. The course of CVD begins at an early age and evolves throughout life. Typically, risk factor precursors (eg, prehypertension, borderline abnormal lipids) are first observed in adolescence or young adulthood. By middle age, they develop into full-fledged cardiometabolic risk factors and subclinical disease, which usually become clinically apparent in older age. Importantly, risk factors for CVD reflect the complex interplay between genetic and environmental factors and demonstrate the complexity of the multiple determinants of disease. Editorial see p 17 Many of the genetic and environmental determinants of CVD have been identified over the past 50 years, and successful preventive and therapeutic strategies have been developed as a result. However, many potential genetic or acquired disease drivers remain unaccounted for, as illustrated by the observation that the major CVD risk factors combined account for only a fraction of the population-attributable risk.1 In addition, variations in CVD risk exist among individuals with similar risk profiles. Part of these differences may reflect differences in profiles of known risk factors that have not yet been fully refined but also individual differences in underlying genetic modifiers of such risk factors. Modern genomics, with its ability to provide ideally unbiased analysis of the entire genome, offers an approach to the ascertainment of all genetic determinants of CVD. Furthermore, the increasingly broad range of “omics” methods, including RNA-Seq, modern proteomics, metabolomics, and metabonomics, provide deeper and more refined molecular detail by which to define an individual’s genome and its relationship to (patho)phenotype. …