DESCRIPTION (provided by applicant): It is now obvious that large samples are essential to make much headway on the genetics of schizophrenia (SCZ). To identify genes that underlie liability to SCZ, we will recruit a large and diverse sample of 1260 African- American families, primarily from the southeastern US, all of whom have at least one member diagnosed with SCZ. A substantial portion of this diverse set of families will contribute to standard Affected Sibling and Relative Pair linkage analysis and to Quantitative Trait Locus (QTL) analyses of neurocognitive traits; the entire sample will be used for admixture mapping in candidate regions of interest This project also lays the foundation for QTL analysis by examining genetic influences on cognitive abilities among persons affected by SCZ and their extended family members. This minority sample would be impossible to recruit without multiple participating sites using the same protocol. Eight institutional sites have teamed up under the Collaborative ROls for Clinical Studies of Mental Disorders to accomplish this goal. The collaboration marries expertise in diagnoses, neurocognitive assessments, family recruitment, and genetic analyses. Substantial samples and refined, multivariate phenotypes should combine to give unprecedented power to determine susceptibility genes for this disease. Our study design is motivated by several considerations. The time is ripe for merging finer phenotypic information with rigorous diagnosis, and the analytic tools are in place, both for finer phenotypic characterization and the joint analysis of phenotypes and genotypes. In terms of mental health, African Americans are an underserved population. The genetic basis of SCZ in the African-American population must have its roots in both Africa and Europe. if the liability alleles for SCZ were different on the two continents, either in kind or frequency, then what we learn from the study of peoples of European ancestry will not necessarily transfer seamlessly to the African population and, by extension, to the African-American population. Therefore it is essential to study SCZ genetics in African-American populations. Finally, we have an outstanding track record of African American participation in research studies, and a deep appreciation of their population genetics.
- National Institute of Mental Health
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