Strategies for linkage studies of schizophrenia: pedigrees, DNA markers, and statistical analyses

A current overview of the genetics of schizophrenia is presented. Recently reported linkage studies of schizophrenia using polymorphic DNA markers are discussed and critically evaluated. Linkage studies of schizophrenia that we are currently undertaking are described, and the rationale underlying the specific strategies that we are using is explained. Our major focus is on extended pedigrees ascertained in Ireland containing a high density of schizophrenic cases, but we are also planning to use the technique of homozygosity mapping in an attempt to localize a recessively inherited gene that may be segregating in consanguineous families ascertained in Saudi Arabia. Issues relating to diagnostic criteria, the choice of which DNA markers to type with the highest priority, and appropriate statistical methodology are also considered.