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）：这是一种申请，以收集来自荷兰相对同质人群的2500名躁郁症（BP）患者的大量队列。对这些患者进行了广泛的表型，其中包括用于纵向评估双极疾病的生活形式。对于选择性的组活性度量和大脑成像数据（MRI），将获得。除了收集用于DNA和RNA提取的血液外，所有受试者还将同意参加NIMH人类遗传学计划，以生成可用于科学界可以使用的淋巴细胞细胞系。我们还将收集可用父母的DNA和BP概率的兄弟姐妹，以进行后续遗传研究。由于鉴定神经精神特征的遗传敏感性基因需要非常大的样本量，因此，荷兰国家BP患者的荷兰国家登记量是n> 8,000名额外的BP患者作为表型信息和基础设施的资源，以收集更大数量的生物材料。该应用程序补充了正在进行的NIMH资助的精神分裂症全基因组协会研究（GWAS）对同一人群的研究，这是UCLA和UMC UTRECHT（荷兰）的同一研究小组的合作努力。使用同一组临床医生以及相同的遗传均质种群来研究双相情感障碍和精神分裂症，这为对两种表型的比较分析提供了独特的机会，这反过来又有助于鉴定重叠以及独特的候选遗传性因素。 GWA将使用收集的探针和已经可用的荷兰控制（n> 10,000）进行。基因表达分析数据的分析将补充遗传分析。这项研究将与神经精神特征的荟萃分析完全融合，并将基因组数据提供给科学界。 公共卫生相关性：此应用是研究来自欧洲相对同质人群的大量患者的双相情感障碍的遗传基础。同一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，因此我们的研究为这些神经精神疾病的差异和重叠特征提供了独特的机会。