Metabolic traits as intermediate phenotypes

Complex diseases such as coronary heart disease or diabetes mellitus are influenced by a large number of genes and environmental factors. Therefore, in most cases the contribution of a single gene is small. The identification of these genes requires a large number of well characterized patients and controls. Alternatively, the investigation of intermediate phenotypes instead of these complex endpoints seems to be more promising. An intermediate phenotype which is usually already well known or suspected to be associated with the investigated disease, is heritable and represents an aspect among others in the pathogenesis of the complex disease. This results in an accentuation of the phenotype and reduction of genetic heterogeneity. The investigation of the genetics of the intermediate phenotype instead of investigating the genetics of the final endpoints allows the elucidation of this aspect of the disease. Optimal intermediate phenotypes are quantitative, easy to measure biochemical parameters. This results in an increased statistical power in contrast to qualitative phenotypes.