Genetic principles and methods in high-risk studies of schizophrenia

Recent advances in genetic epidemiology present excellent opportunities for future high-risk studies of schizophrenia. Improved methods are now available for specifying the natural boundaries of the schizophrenia spectrum and evaluating the mode of inheritance of schizophrenia and its biosocial risk factors. Path-analytic techniques permit the derivation of multifactor indices of both biological and social antecedents of schizophrenia. Powerful advances have been made in segregation analysis of pedigree data and in the power of linkage tests with DNA markers to confirm the presence of putative major loci that influence susceptibility to complex phenotypes like schizophrenia. The yield of information from high-risk samples is greatly increased when both longitudinal and pedigree analyses are combined.