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

描述（由申请人提供）：这是一项从荷兰相对同质的人群中收集2,500名双相情感障碍（BP）患者的大型队列的申请。对这些患者进行了广泛的表型分析，包括用于双相情感疾病纵向评估的生命表;对于选择性组，将获得活动测量和脑成像数据（MRI）。除了采集用于DNA和RNA提取的血液外，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淋巴母细胞系。我们还将收集BP先证者的父母和兄弟姐妹的DNA，用于后续遗传研究。由于神经精神性状的遗传易感基因的鉴定需要非常大的样本量，因此正在提出一个荷兰国家BP患者登记册，其中n> 8，000名额外的BP患者作为表型信息的资源和基础设施，以收集更大数量的生物材料。该申请补充了正在进行的NIMH资助的精神分裂症全基因组关联研究（GWAS），该研究是UCLA和UMC Utrecht（荷兰）相同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进行双相情感障碍和精神分裂症的研究提供了一个独特的机会，进行比较分析的两种表型，这反过来又有利于识别重叠以及独特的候选遗传易感因素。将使用收集的先证者和已有的荷兰对照（n> 10，000）进行GWAS。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病学特征的荟萃分析的内部努力充分整合，基因组数据将提供给科学界。

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.