PHASE II COOPERATIVE AGREEMENT FOR GENETICS STUDIES

本申请是对RFA MH 94-10“第二阶段合作”的回应。 双相情感障碍和精神分裂症的遗传学研究协议。" 在第一阶段，被称为“诊断中心， 精神病学联系研究”，临床数据和DNA（包括细胞 线）已经在四个中心使用共同的方案收集。一 共有140个家庭至少有两个双相I型先证者， 收集。 这项建议的目的是确定参与家族性疾病的基因。 躁郁症正在进行的合作将得到扩展， 对第一阶段收集的家系进行基因分型， 分析。在第二阶段，四个中心将继续分工 平等地 我们将采用三阶段方法进行基因分型。在阶段la中 基因组调查将以7厘摩的间隔在面板上进行 在524例具有双相表型或需要 建立阶段。这个小组被选中是为了最大限度地利用 受影响的同胞对和受影响的谱系成员的方法。 还将使用参数（LOD评分）方法。 将包括在第一阶段之后收集的新家庭。使用此 更强大的样本，基于Stage的感兴趣的染色体区域 l将对实地的调查结果和报告采取后续行动。 在第III阶段，样本将扩大到包括受试者的 复发性单相情感障碍LOD评分分析将在 这一扩大谱系的样本，目的是跟踪有希望的 第一阶段和第二阶段的结果。 我们将进行模拟我们的血统，以确定最 强大的分析方法测试的联系和异质性。 此外，我们将利用丰富的临床数据集， 测试这个复杂表型的各种定义。 最后，我们将开发一个档案数据库，供科学研究人员使用。 如U O 1合同中所述。

This application is a response to RFA MH 94-10 "Phase Two Cooperative Agreement for Genetic Studies of Bipolar Disorder and Schizophrenia." During Phase 1, known as "Diagnostic Centers for Psychiatric Linkage Studies," clinical data and DNA (including cell lines) have been collected at four centers using a common protocol. A total of 140 families with at least two bipolar I probands have been collected. The purpose of this proposal is to identify genes involved in familial bipolar disorder. The ongoing collaboration will be extended in order to genotype the families collected in Phase 1 and perform linkage analyses. In Phase 2, the four centers will continue to divide the work equally. We will employ a three stage approach to genotyping. In Stage l a genomic survey will be performed at 7 centiMorgan intervals on a panel of 524 subjects who have bipolar phenotypes or who are needed to establish phase. This panel has been selected to take maximal advantage of the affected sib-pair and affected pedigree member methods. Parametric (LOD-score) methods will also be used.The Stage II panel will include new families that were collected after Stage I. Using this more powerful sample, chromosomal regions of interest based on Stage l findings and reports from the field will be followed up. In Stage III, the sample will be expanded to include subjects' with recurrent unipolar disorder. LOD-score analyses will be performed on this sample of enlarged pedigrees with the goal of following promising findings from stages I and II. We will perform simulations of our pedigrees to determine the most powerful analytical methods of testing for linkage and heterogeneity. In addition, we will utilize the rich clinical data set in order to test various definitions of this complex phenotype. Finally, we will develop an archival database for use by the scientific community as detailed in the U O1 contracts.