Expanding Rapid Ascertainment Networks of Schizophrenia Families in Taiwan

This proposal responds to Request for Applications RFA ( Rapid Founding Award)-MH ( Mental Health)-08-131, which seeks applications that propose to enrich pre-existing resources for schizophrenia in the NIMH ( National Institute of Mental Health) Human Genetics Initiative and to apply genomic methods to further our 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 SNP scanning. We, thus, collaborate with Professor Ming T, Tsuang and his extended subcontracted researchers to apply for this project. We, the research team in Taiwan, will collect 3800 trio families (11400 subjects) of schizophrenia. In our recently completed NIMH-funded Genetic Linkage Study of Schizophrenia (R01MH059624; USA PI: Ming T. Tsuang; Taiwan PI: Hai-Gwo Hwu), the investigators established a large and efficient ascertainment network and infrastructure in Taiwan, which will again be utilized and expanded in the proposed study. 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. 1.Rapidly ascertain schizophrenia trio families from ten Taiwanese clinical ascertainment sites;
2. 2.Supplement NIMH Genetics Initiative collections by sending all clinical data and biomaterials to the appropriate repositories;
3. 3.Assess the association of schizophrenia with a genome-wide panel of single-nucleotide polymorphisms (SNPs) and their constituent haplotypes;
4. 4.Analyze quantitative schizophrenia phenotypes such as age at onset ;
5. 5.Perform a genome-wide survey for copy-number variations related to schizophrenia;
6. 6.Test for gene-gene interactions (epistasis); and
7. 7.Test for gene-environment interactions, such as the well-established effect of season of birth.