International Cohort Collection for Bipolar Disorder

描述（由申请人提供）：双相情感障碍（BPD）是一个重要的公共卫生优先事项，造成了巨大的残疾负担、个人痛苦和经济成本。遗传易感性是已知的BPD最强的危险因素，特异性易感性基因的鉴定将对推进我们对BPD生物学的理解和揭示新的治疗靶点具有巨大的意义。迄今为止，BPD遗传研究的有限成功是由于其复杂的遗传结构，可能包括许多影响不大的贡献位点。近年来，群体遗传学和基因分型技术的进步使得像BPD这样的复杂疾病的遗传解剖成为一项可行的项目。全基因组关联研究（GWAS）已经确定了一系列其他常见医学疾病的易感性变异。然而，很明显，要实现BPD的成功，需要比目前可用的样本大得多的样本。该申请是一个国际研究联盟对RFA-MH-08-130：“双相情感障碍和精神分裂症的基因组分析：美国和全球大型队列研究”的回应。拟议的国际双相情感障碍队列收集（ICCBD）将通过建立一个独特的BPD个体样本和数据的大型收集来解决大规模DNA和数据资源的需求。该应用程序的具体目的是：1)在美国两个地点（波士顿和洛杉矶），使用新颖的高通量表型分析方法，确定并收集5年内大量BPD病例（N = 9000）和未受影响的对照组（N = 9000）；2)将来自美国病例对照样本的表型数据与来自英国和瑞典的平行的、单独资助的欧洲病例对照样本（10,000例病例和10,000对照）相结合，构建一个统一的遗传研究数据资源。对这些资源进行单独资助的基因分型和遗传分析，将充分表征整个样本中的常见多态性和拷贝数变异，以检测新的风险变异，并尝试复制最引人注目的先前发现。这一资源，加上现有的样本，将为发现BPD的遗传决定因素提供一个前所未有的平台。双相情感障碍（BPD）是一个主要的公共卫生重点，造成了巨大的残疾负担、个人痛苦和经济成本。遗传易感性是已知的BPD最强的危险因素，特异性易感性基因的鉴定将对推进我们对BPD生物学的理解和揭示新的治疗靶点具有巨大的意义。迄今为止，BPD遗传研究的有限成功是由于其复杂的遗传结构，可能包括许多影响不大的贡献位点。拟议的国际双相情感障碍队列收集（ICCBD）将通过建立一个独特的BPD个体样本和数据的大型收集来解决大规模DNA和数据资源的需求。

DESCRIPTION (provided by applicant): Bipolar disorder (BPD) is a major public health priority, responsible for a vast burden of disability, personal suffering, and economic cost. Genetic susceptibility is the strongest known risk factor for BPD, and the identification of specific susceptibility genes would have enormous implications for advancing our understanding of the biology of BPD and revealing novel targets for treatment. The limited success to date of genetic studies of BPD has been due to its complex genetic architecture that likely includes many contributing loci of modest effect. Advances in population genetics and genotyping technologies have recently made the genetic dissection of complex disorders like BPD a feasible project. Genomewide association studies (GWAS) have already identified susceptibility variants underlying a range of other common medical disorders. However, it has become clear that much larger samples than are currently available will be needed to achieve such successes for BPD. This application is a response by an international consortium of investigators to RFA-MH-08-130: "Genomic Parsing of Bipolar Disorder and Schizophrenia: Studies of Large Cohorts in the U.S. and Across the Globe." The proposed International Cohort Collection for Bipolar Disorder (ICCBD) will address the need for large-scale DNA and data resources by establishing a uniquely large collection of samples and data from individuals with BPD. The specific aims of this application are 1) to ascertain and collect a large cohort of BPD cases (N = 9000) and unaffected controls (N = 9000) over five years at two U.S. sites (Boston and Los Angeles) using novel high-throughput phenotyping methods; and 2) to construct a harmonized data resource for genetic studies combining phenotypic data from the U.S. case-control sample with a parallel, separately funded European case-control sample (10,000 cases and 10,000 controls) obtained from the UK and Sweden. Separately funded genotyping and genetic analyses of these resources will fully characterize common polymorphisms and copy number variants in the full sample to detect novel risk variants and attempt replication of the most compelling prior findings. This resource, augmented by existing samples, will provide an unprecedented platform for the discovery of the genetic determinants of BPD. Bipolar disorder (BPD) is a major public health priority, responsible for a vast burden of disability, personal suffering, and economic cost. Genetic susceptibility is the strongest known risk factor for BPD, and the identification of specific susceptibility genes would have enormous implications for advancing our understanding of the biology of BPD and revealing novel targets for treatment. The limited success to date of genetic studies of BPD has been due to its complex genetic architecture that likely includes many contributing loci of modest effect. The proposed International Cohort Collection for Bipolar Disorder (ICCBD) will address the need for large-scale DNA and data resources by establishing a uniquely large collection of samples and data from individuals with BPD.