Molecular Genetic Study of Schizophrenia: Parent-Offspring Trios

Schizophrenia is a chronic and devastating major psychiatric disorder. Family, twin, and adoption studies indicated that schizophrenia has a significant genetic component. The mode of transmission is still not clear and a multilocus model was proposed. The location of susceptibility gene of schizophrenia is still under active search using molecular genetic methods. We propose to collect genomic DNA and lymphoblast cell lines of a total of 150 DSM-IV schizophrenic patients and their first degree relatives including parents (parent-offspring trios) and non-affected siblings in three years. Adequate statistical power of molecular genetic studies is a great concern. For this concern, we will examine the patients and their parents clinically by using the Diagnostic Interview for Genetic Studies (DIGS) for diagnostic assessment, and by using neuropsychological battery including sustain attention, executive function, verbal memory and general intelligence for neuropsychological evaluations. The project is feasible because (1) The PI and his research team have experience in successfully collecting co-affected sib-pair families of schizophrenia and in setting-up molecular genetic laboratory in the past decade. We are experienced and competent to execute this project. (2) The PI and his research team have established the instruments using to clarify the phenotypes including the DIGS, the neuropsychological battery these years. Major goals of this project are: (1) to cooperate with this important Taiwan Genotype Consortium proposed by the NHRI; (2) to detect major schizophrenia susceptibility genes related to the neuropsychological endophenotype; (3) to do further fine mapping on suggestive linkage markers to replicate previous linkage studies results using our previously-collected co-affected sib-pair family sample; and (4) to deposit the lymphoblast cell lines into NHRI Cell Bank serving as a national resource for basic research in Taiwan.