[Genetic markers and risk factors in diseases with complex etiology: psychiatric diseases]

The goal of this paper is to show how the information provided by genetic markers may help to delineate the genetic factors implicated in the aetiology of mental disorders. Family studies have provided good evidence for the involvement of genetic factors in the aetiology of two of the most common psychiatric diseases: affective disorders and schizophrenia. However, a single susceptibility gene responsible for all the familial resemblance for these diseases is unlikely. Analysis of the disease transmission in families has been, so far, unsuccessful in delineating a genetic component in their aetiology. With the recent development of molecular genetics a large number of genetic markers are now available. They allow an alternative investigation of the genetic aetiology of such disease. Indeed a non independent transmission of the disease is evidence for 1) the effect of at least one susceptibility gene and 2) the genetic localization of this gene on the same chromosome and near the marker. However, linkage strategies in psychiatric disorders face specific difficulties that should not be ignored. For such complex diseases, the observed disease correlations between relatives are likely due to the effect and to the interaction of both genetic and non genetic factors. Accurate analysis of genetic linkage requires consideration of residual (non-genetic) familial correlations in the joint segregation of the disease and the marker. Furthermore, focusing linkage strategies on markers of candidate genes would clearly enhance the power of the linkage test.