Indicators of liability to schizophrenia: perspectives from genetic epidemiology

Research in genetic epidemiology has provided powerful evidence that genetic factors contribute to the familial transmission of schizophrenia. However, the precise mode of inheritance has not been elucidated, and no disease-susceptibility locus has been identified. Genetically complex illnesses such as schizophrenia can be characterized by multiple intermediate correlated traits or risk factors that likely play important roles in the susceptibility of individuals to developing the illness. Such biobehavioral traits potentially associated with liability to schizophrenia have been carefully studied by experimental psychopathologists and are discussed in this issue. This article discusses how correlated trait data collected from probands and their relatives can complement diagnostic assessments and offer promise for greatly enhancing the informativeness of pedigrees for genetic analysis and for facilitating replication of linkage findings. The results of analyses of simulated and real data discussed here suggest that assessment of biobehavioral traits with the greatest validity and cost-effectiveness should be required in the next generation of linkage and other genetic studies in schizophrenia.