Schizophrenia Liability Genes Among African Americans

描述（由申请人提供）：现在很明显，大样本对于精神分裂症（SCZ）遗传学的重大进展至关重要。为了识别导致SCZ易感性的基因，我们将招募1260个非裔美国家庭的大样本，这些家庭主要来自美国东南部，所有家庭中至少有一名成员被诊断出患有SCZ。这些不同的家系中的相当一部分将有助于标准的受累同胞和相对配对连锁分析以及神经认知性状的数量性状基因座（QTL）分析;整个样本将用于感兴趣的候选区域的混合作图。该项目还通过检查SCZ患者及其大家庭中对认知能力的遗传影响，为QTL分析奠定了基础。成员如果没有使用相同方案的多个参与研究中心，则不可能招募该少数样本。为了实现这一目标，八个机构网站在精神疾病临床研究合作ROLS下进行了合作。这项合作结合了诊断、神经认知评估、家庭招募和遗传分析方面的专业知识。大量的样本和精炼的、多变量的表型应该联合收割机结合起来，以提供前所未有的力量来确定这种疾病的易感基因。 我们的研究设计是出于几个考虑。将更精细的表型信息与严格的诊断相结合的时机已经成熟，分析工具已经到位，既可以进行更精细的表型表征，也可以对表型和基因型进行联合分析。在心理健康方面，非裔美国人是一个服务不足的群体。非裔美国人中SCZ的遗传基础必须起源于非洲和欧洲。如果SCZ的易感等位基因在两大洲的种类或频率不同，那么我们从欧洲血统人群的研究中所了解到的不一定会无缝地转移到非洲人群中，并延伸到非洲裔美国人中。因此，在非裔美国人群体中研究SCZ遗传学是必要的。最后，我们有一个非洲裔美国人参与研究的杰出记录，并对他们的人口遗传学的深刻赞赏。

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.