This proposal responds to Request for Applications RFA-MH-08-131, which seeks applications that propose to enrich pre-existing resources for schizophrenia in the National Institute of Mental Health (NIMH) Human Genetics Initiative and to apply genomic methods to further the investigators understanding of the molecular etiology of the disorder. The overarching aims of this proposal are to quickly and cost-effectively ascertain a large sample of trio families affected by schizophrenia, and to discover causal variants for the disorder in the first family-based genome-wide association study (GWAS) of the disorder. In Taiwan, there is no such kind of policy to support this kind of GWAS study as it is a very expensive study, including collecting large family samples and genome-wide single-nucleotide polymorphism (SNP) scanning. The investigators, thus, collaborate with Professor Ming T, Tsuang and his entended subcontracted researchers to apply for this project. The investigators, the research team in Taiwan, will collect 3800 trio families (11400 subjects) of schizophrenia. Through additional ascertainment within this framework, the investigators will collect an aggregate sample with adequate power for detecting in a GWAS those variants that make even small contributions to the risk for the disorder.
The investigators will meet the overarching goals of this project by accomplishing several Specific Aims, as follows: 1) Rapidly ascertain schizophrenia trio families from Taiwanese clinical ascertainment sites; 2) Supplement NIMH Genetics Initiative collections by sending all clinical data and biomaterials to the appropriate repositories; 3) Assess the association of schizophrenia with a genome-wide panel of single-nucleotide polymorphisms (SNPs) and their constituent haplotypes; 4) Analyze quantitative schizophrenia phenotypes such as age at onset ; 5) Perform a genome-wide survey for copy-number variations related to schizophrenia; 6) Test for gene-gene interactions (epistasis); and 7) Test for gene-environment interactions, such as the well-established effect of season of birth.