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)的遗传学研究取得很大进展是必不可少的。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样本和多样化样本，这些家庭主要来自美国东南部，他们都至少有一名成员被诊断为SCZ。这组不同的家系中有相当一部分将对标准的受影响同胞和相对配对连锁分析以及神经认知特征的数量性状基因座(QTL)分析做出贡献；整个样本将用于候选感兴趣区域的混合作图。该项目还通过检测受SCZ影响的人及其家族成员的认知能力的遗传影响，为QTL分析奠定了基础。如果没有多个参与网站使用相同的方案，这个少数样本是不可能招募的。八个机构网站已经在精神疾病临床研究合作名单下合作，以实现这一目标。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。大量的样本和精炼的、多变量的表型应该结合在一起，赋予确定这种疾病的易感基因前所未有的力量。 我们的研究设计是出于几个方面的考虑。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。非裔美国人群体中SCZ的遗传基础必须植根于非洲和欧洲。如果SCZ的易感等位基因在两个大陆上不同，无论是在种类上还是在频率上，那么我们从欧洲血统民族的研究中学到的东西不一定会无缝地转移到非洲人口，进而转移到非洲裔美国人。因此，对非裔美国人群体中SCZ基因的研究是非常必要的。最后，我们在非洲裔美国人参与研究研究方面有着出色的记录，并对他们的群体遗传学有着深刻的理解。

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.