Genome-wide association (GWA) is widely viewed as the most powerful, systematic and unbiased genetic approach to the study of the common disease/common variant (CDCV) hypothesis of complex disorders like schizophrenia. We propose to conduct a single- stage GWA study of schizophrenia in an ethnically homogeneous sample previously collected in Ireland. The sample of 2357 affected individuals and 2000 or 5000 controls provides considerable power to detect genes of modest effect. Our overall goal is to contribute to the conclusive identification of genetic variation that influences the liability to schizophrenia. In order to achieve this, we plan to 1) collect 900,000 individual DNA polymorphism genotypes for each member of the sample, 2) perform a primary analysis of this data for association with schizophrenia, and in secondary analyses to 3) assess weighted significance testing based on prior genetic or biological data, other phenotype data available and clinical features of illness, and 4) assess multi-locus, pathway and system associations, and 5) to recontact, reconsent and resample the affected individuals for contribution to the NIMH repository.
Schizophrenia is a common and often severe mental illness with a population frequency of ~1 percent;substantial numbers of individuals in the US or other populations are affected. The illness is a major public health burden because of the early onset, non-fatal course and need for long-term care for many patients.
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