Schizophrenia Liability Genes Among African Americans

描述（由申请人提供）：现在很明显，要在精神分裂症（SCZ）的遗传学上取得很大进展，大样本是必不可少的。为了确定导致SCZ的基因，我们将招募1260个非洲裔美国家庭的大量不同样本，主要来自美国东南部，所有家庭至少有一名成员被诊断患有SCZ。这一多样化的家族的很大一部分将有助于标准的影响兄弟姐妹和亲属对连锁分析和神经认知特征的数量性状位点（QTL）分析；整个样本将用于候选感兴趣区域的混合定位。该项目还为QTL分析奠定了基础，通过检查SCZ患者及其大家庭成员对认知能力的遗传影响。如果没有使用相同协议的多个参与站点，就不可能招募到这些少数样本。为了实现这一目标，八家机构已经在精神疾病临床研究合作项目下联合起来。这项合作结合了诊断、神经认知评估、家庭招募和基因分析方面的专业知识。大量的样本和精细的多变量表型相结合，将为确定这种疾病的易感基因提供前所未有的力量。

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.