3/3 Genetic Analysis of the International Cohort Collection for Bipolar Disorder

 描述（由申请人提供）： 该赠款，“双相情感障碍国际队列收集的遗传分析”，是一个长期的合作努力的继续，为响应RFA的样本收集在双相情感障碍。因此，我们正在提交来自原始调查小组的当前新申请，以继续合作，并继续进行下一个逻辑步骤，分析正在生成的数据。我们根据NIMH FOA MH 08 -130制定了“双相情感障碍国际队列收集”。在R 01 MH 085542（Smoller/Sklar，PI）和慈善基金的赞助下，我们实施了一种表型稳健、快速且具有成本效益的样品收集方法。在五年的资助期间，我们已经从以前从未用于双相情感障碍（BD）基因组研究的约18，000例病例和16，000例对照中提取了DNA。我们在这里提出了一个独特的样本增强目标，以增加我们的知识BD和保持这个高生产力的团队完好无损。这里研究的样本将是GWAS可用样本的两倍多，并且将是第一批使用外显子组芯片和外显子组测序分析罕见变异的样本。这些分析将为检测赋予BD风险的网络和位点提供显著增强的能力。在目标1中，我们将对15，800例病例和18，598例对照的独立队列进行基因组表征，以通过常见单核苷酸多态性、拷贝数变异和罕见单核苷酸变异的关联研究来识别BD风险的高置信度遗传位点。我们将进一步使用这些数据来探索两种特定临床情况下BD的遗传预测模型。在目标2中，我们将通过检查表型亚组、交叉障碍关系、定量人格维度和神经认知来应用这些数据来表征基因型-表型关系的谱。我们的目标是更多地了解BD的遗传学以及基因如何改变疾病风险。我们建议使用该领域中最大和最全面研究的样本收集，包括遗传和表型风险因素。

 DESCRIPTION (provided by applicant): The grant, "Genetic Analysis of the International Cohort Collection for Bipolar Disorder", is continuation of a long-standing collaborative effort funded in response to an RFA for sample collections in bipolar disorder. We are thus submitting the current new application from the original group of investigators to continue the collaboration and proceed to its next logical step analyses of data being generated. We developed the "International Cohort Collection for Bipolar Disorder" in response to a NIMH FOA MH08-130. Under the auspices of R01MH085542 (Smoller/Sklar, PIs) and philanthropic funding we implemented a phenotypically robust, rapid, and cost effective method for sample collection. During the five years of the grant we have banked DNA from ~18,000 cases and 16,000 controls never previously used for genomic study of bipolar disorder (BD). We propose here enhanced aims in a unique sample to increase our knowledge of BD and to keep this highly productive team intact. The samples studied here will more than double the available samples for GWAS, and will be among the first to analyze rare variants using exome chip and exome sequencing. These analyses will provide substantially enhanced power for detection of networks and loci that confer BD risk. In Aim 1 we will perform a genomic characterization of an independent cohort of 15,800 cases and 18,598 controls to identify high confidence genetic loci for risk of BD through association study of common single nucleotide polymorphisms, copy number variants, and rare single nucleotide variants. We will further use the data to explore genetic prediction models for BD for two specific clinical scenarios. In Aim 2 we will apply these data to characterize the spectrum of genotype-phenotype relationships by examining phenotypic subgroups, cross- disorder relationships, quantitative personality dimensions, and neurocognition. Our goal is to learn more about the genetics of BD and how genes might act to alter disease risk. We propose to do this using the largest and most comprehensively studied sample collection in the field that includes both genetic and phenotypic risk factors.