Genome-Wide Association Study of Schizophrenia

描述(由申请人提供)：这是根据RFA-MH-07-060，“NIMH(R01)全基因组协会数据分析申请的有限竞争”，为R01站点提交的为期一年的资金申请。这一建议的基础是，由于SZ的病理生理学尚不清楚，但可能涉及多种遗传成分，将全基因组关联策略应用于具有足够统计能力的临床样本，有望识别连锁分析和候选基因关联研究遗漏的易感基因。具体目标是：1)在1,540名欧洲血统(EA)病例和1,540名筛选对照对象中的全基因组SNP图谱，以及从基于存储库的精神分裂症(MGS)分子遗传学(MGS)样本中的1,100名非裔美国人(AA)病例和1,100名AA对照中进行基因分型，该样本由10个地点按照共同的方案收集，证明了评价者间诊断和临床评分的可靠性。2)对性状的遗传关联进行一次和二次分析，考虑群体亚结构和杂交种的影响。3)根据遗传关联信息网(Gain)的政策，我们将快速共享基因数据和大型表型数据集。病例和对照的所有DNA样本和临床数据已经可用于GAIN实验，并由NIMH存储库计划(www.nimhqenetics.org)使用其标准的中央数据库管理系统公开提供，以便其他科学家能够使用这些样本和临床数据来检查、确认和扩展我们的发现。这项应用的总体目标是寻找精神分裂症的新易感基因。

DESCRIPTION (provided by applicant): This is an application for 1 year of funding for an R01 site submitted under RFA-MH-07-060, "Limited Competition for Applications to Analyze Whole Genome Association Data for NIMH (R01)." The rationale underlying this proposal is that since the pathophysiology of SZ is unknown, but is likely to involve multiple genetic components, application of the genome-wide association strategy to clinical samples with adequate statistical power is expected to identify susceptibility genes that have been missed by linkage analysis and by candidate gene association studies. The Specific aims are: 1) Genotype a genome-wide SNP map in 1,540 cases and 1,540 screened control subjects of European ancestry (EA), and 1,100 African American (AA) cases and 1,100 AA controls from the repository-based Molecular Genetics of Schizophrenia (MGS) sample collected by ten sites under a common protocol with demonstrated inter-rater reliability for diagnosis and clinical ratings. 2) Carry out primary and secondary analyses of genetic association of the trait, accounting for population substructure and admixture. 3) In concordance with Genetic Association Information Network (GAIN) policies, we will rapidly share the genotypic data and a large phenotypic dataset. All DNA specimens and clinical data for cases and controls are already available for the GAIN experiments and are being made publicly available by the NIMH repository program (www.nimhqenetics.org)using its standard centralized database management system, so that other scientists will be able to use these specimens and clinical data to check, confirm, and extend our findings. The overall goal of this application is to find new susceptibility genes for schizophrenia.