Search for new thrombosis-related genes through intermediate phenotypes. Genetic and household effects

As a complex disease, thrombosis is determined by environmental and genetic factors and by the interaction of these factors. One of the objectives of modern epidemiology is to understand the underlying complexity in complex diseases by means of disentangling the genetic from the environmental factors and quantifying the relative influence of each factor on the disease. Often it is easier and more fruitful to study intermediate phenotypes than the diseases themselves. The first step of these analyses is to determine the relative contributions of genes (heritability), measured environmental factors that are specific to an individual, and environmental factors that are shared by members of a household (household effects), to variation in the complex phenotype. Currently there are published data on 56 phenotypes involved in these kind of genetic studies of hemostasis and potentially related to thromboembolic disease. The main conclusion of these studies is that genetic effects (as measured by heritabilities) are major contributors to the phenotypic variability. Only in 16 of the 56 (29%) of the studied phenotypes, were household effects reported. These results are primordial in the design of further studies consisting in wide-genome explorations in the search for the underlying genes.