Genomic Studies of Bipolar Disorder in a Large Cohort from The Netherlands

荷兰大群体双相情感障碍的基因组研究

• 批准号: 8114989
• 负责人: Roel A Ophoff
• 金额: $ 79.02万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-21 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8114989
• 关键词: Biocompatible Materials; Biopsy; Bipolar Disorder; Blood; Blood specimen; Brain imaging; Cell Line; Characteristics; Circadian Rhythms; Clinical assessments; Communities; Complement; Consent; DNA; DSM-IV; Data; Data Analyses; Data Set; Diagnosis; Disease; European; Fibroblasts; First Degree Relative; Funding; Future; Gene Expression; Gene Expression Profiling; Generations; Genetic; Genetic Predisposition to Disease; Genetic Variation; Genomics; Goals; Human Genetics; Image; Internet; Life; Link; Magnetic Resonance Imaging; Measures; Meta-Analysis; Methods; National Institute of Mental Health; Netherlands; Parents; Participant; Patients; Pattern; Phenotype; Plasma; Population; Population Study; Predisposition; Protocols documentation; RNA; Recruitment Activity; Relative (related person); Research; Research Infrastructure; Research Personnel; Resources; Sample Size; Sampling; Schedule; Schizophrenia; Siblings; Single Nucleotide Polymorphism; Skin; Susceptibility Gene; Variant; base; cohort; comparative; data sharing; database of Genotypes and Phenotypes; density; follow-up; genetic analysis; genome wide association study; genome-wide; indexing; lymphoblastoid cell line; neuropsychiatry; peripheral blood; proband; public health relevance; repository; trait

DESCRIPTION (provided by applicant): This is an application to collect a large cohort of 2,500 bipolar disorder (BP) patients from a relatively homogeneous population in The Netherlands. These patients are extensively phenotyped including a life-chart for longitudinal assessment of bipolar illness; for a selective group activity measures and brain imaging data (MRI) will be obtained. In addition to collecting blood for DNA and RNA extraction, all subjects will be consented for participation in the NIMH Human Genetics Initiative for generation of lymphoblastoid cell lines that are made available to the scientific community. We will also collect DNA of available parents and siblings of BP probands for follow-up genetic studies. Since the identification of genetic susceptibility genes for neuropsychiatric traits requires very large sample sizes, a Dutch national register of BP patients is being proposed with n>8,000 additional BP patients as a resource for phenotype information and infrastructure to collect biomaterials of even larger numbers. This application complements the ongoing NIMH-funded schizophrenia genome-wide association study (GWAS) in the same population, a collaborative effort of the same research groups at UCLA and UMC Utrecht (The Netherlands). The use of the same group of clinicians as well as the same genetically homogeneous population for the study of bipolar disorder and schizophrenia provides a unique opportunity to perform comparative analyses of both phenotypes, which will in turn facilitate the identification of overlapping as well as distinctive candidate genetic susceptibility factors. GWAS will be performed using collected probands and already available Dutch controls (n>10,000). Analysis of gene expression profiling data will compliment the genetic analyses. This study will fully integrate with the internal efforts of meta-analyses of neuropsychiatric traits and genomic data will be made available to the scientific community. PUBLIC HEALTH RELEVANCE: This application is to study the genetic basis of bipolar disorder in a large group of patients from a relatively homogeneous European population. The same population is already being used for a similar schizophrenia study. Since these diseases are known to be related and yet have different characteristics, our study provides a unique opportunity to systematically study differences and overlapping features of these neuropsychiatric disorders.

描述（由申请人提供）：这是一个从荷兰相对同质的人群中收集 2,500 名双相情感障碍 (BP) 患者的大型队列的应用程序。这些患者进行了广泛的表型分析，包括用于双向情感障碍纵向评估的生命图；将获得选择性团体活动测量和脑成像数据（MRI）。除了采集血液进行 DNA 和 RNA 提取外，所有受试者都将同意参与 NIMH 人类遗传学计划，以生成可供科学界使用的类淋巴母细胞系。我们还将收集 BP 先证者现有父母和兄弟姐妹的 DNA，用于后续遗传学研究。由于识别神经精神性状的遗传易感基因需要非常大的样本量，因此建议荷兰国家 BP 患者登记册中包含超过 8,000 名额外的 BP 患者，作为表型信息和基础设施的资源，以收集更多数量的生物材料。该应用程序补充了 NIMH 资助的同一人群中正在进行的精神分裂症全基因组关联研究 (GWAS)，该研究是加州大学洛杉矶分校和 UMC Utrecht（荷兰）的同一研究小组的合作成果。使用同一组临床医生以及相同的遗传同质人群来研究双相情感障碍和精神分裂症，为对两种表型进行比较分析提供了独特的机会，这反过来将有助于识别重叠和独特的候选者遗传易感因素。 GWAS 将使用收集的先证者和已有的荷兰对照（n>10,000）进行。基因表达谱数据的分析将补充遗传分析。这项研究将与神经精神特征荟萃分析的内部工作完全结合，基因组数据将提供给科学界。 公共卫生相关性：本申请旨在研究来自相对同质的欧洲人群的一大群患者的双相情感障碍的遗传基础。相同的人群已经被用于类似的精神分裂症研究。由于已知这些疾病是相关的，但具有不同的特征，我们的研究提供了一个独特的机会来系统地研究这些神经精神疾病的差异和重叠特征。