Summary of the American Heart Association’s Scientific Statement on the Relevance of Genetics and Genomics for Prevention and Treatment of Cardiovascular Disease

Abstract

Atherosclerotic cardiovascular disease (CVD) is a major health problem in the United States and around the world.1,2 The development of CVD is a complex process, and evidence demonstrates that family history is associated with CVD.3 There are several mendelian disorders that contribute to CVD, and although the mutations are rare, they have a large relative risk. The most common forms of CVD, however, are believed to be multifactorial and to result from many genes, each with a small effect working alone or in combination with modifier genes or environmental factors. See Circulation. 2007;115:2878–2901 Two main approaches have been used to discover genetic influences on CVD (Figure): genome-wide linkage and gene association studies. For discovery of new genes, the most frequently used method has been genome-wide linkage conducted using genetic and phenotypic data from families. Linkage analysis is a hypothesis-generating method intended to localize genomic regions that might contain genes influencing a trait. Once likely regions have been discovered, efforts shift to identifying the causative genes. Gene maps are scrutinized, and “candidate” genes within regions of interest are identified based on prior knowledge of gene function. Candidate gene association studies are designed to compare genotype frequencies between case and control groups; a statistical difference in frequencies between cases and controls offers evidence that a genotype is associated with the trait. Figure. Fundamentals of the techniques used for the discovery of the genetic basis of CVD. Adapted with permission from: Arnett DK, Baird AE, Barkley RA, Basson CT, Boerwinkle E, Ganesh SK, Herrington DM, Hong Y, Jaquish C, McDermott DA, O’Donnell CJ. Relevance of genetics and genomics for prevention and treatment of cardiovascular disease: a scientific statement from the American Heart Association Council on Epidemiology and Prevention, the Stroke Council, and the Functional Genomics and Translational Biology Interdisciplinary Working Group. …