Role of Genetic Analyses in Cardiology

Abstract

“When a variation is of the slightest use to a being, we cannot tell how much of it to attribute to the accumulative action of natural selection, and how much to the conditions of life.” — Charles Darwin, The Origin of Species, Chapter 5: Laws of Variation, 1859 Genetic testing is a growing discipline in clinical practice, and it is being used to make treatment decisions and to counsel patients. Before genetic testing can be done, reliable information needs to be available on which genes are involved in a disease. Research into genetic determinants of disease often is based on articles reporting the magnitude of the heritability of disease. Here, we address limitations in the use of heritability as a point of departure, such as a basis for power calculations, for genetic studies. Familial aggregation of diseases generally is taken as evidence for a role of genetic factors in the origin of a disorder or trait. A commonly used measure to quantify the extent to which this familial aggregation of diseases is due to genetic factors is the heritability. Heritability estimates were first used by plant and animal breeders to predict the effectiveness of their selection of a desired phenotype such as an increase in milk production or resistance to yeast infections. In human studies, heritability has the intuitive appeal of quantifying genetic effects without necessarily knowing the mode of inheritance of a trait. Heritability is frequently estimated for complex diseases or traits such as diabetes mellitus, coronary artery disease, and serum lipid levels, which are phenotypes reflecting the interplay of genetic and environmental factors. Continuous traits or phenotypes (height, body mass index, serum lipid levels, etc) in a population usually have an approximately normal distribution characterized by a mean and a variance. The total variance can be partitioned mathematically …