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

描述(由申请人提供)：这是一份从荷兰相对同质的人群中收集2500名双相情感障碍(BP)患者的申请。这些患者具有广泛的表型，包括用于纵向评估双相情感障碍的生命图；对于有选择的群体，将获得活动测量和脑成像数据(MRI)。除了采集血液用于提取DNA和RNA外，所有受试者都将被同意参加NIMH人类遗传学倡议，以产生淋巴母细胞系，供科学界使用。我们还将收集BP先证者的可用父母和兄弟姐妹的DNA，用于后续的遗传学研究。由于识别神经精神疾病特征的遗传易感基因需要非常大的样本量，荷兰正在提议建立一个全国BP患者登记制度，将n&gt；8000名BP患者作为表型信息来源和基础设施，以收集更多数量的生物材料。这项应用是对NIMH资助的精神分裂症全基因组关联研究(GWAS)在同一人群中正在进行的补充，这是加州大学洛杉矶分校和UMC Utrecht(荷兰)的相同研究小组共同努力的结果。在双相情感障碍和精神分裂症的研究中使用相同的临床医生群体和相同的遗传同质群体提供了一个独特的机会来对这两种表型进行比较分析，这反过来将有助于识别重叠的和独特的候选遗传易感因素。将使用收集到的先证者和已有的荷兰对照(n&gt；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结合，并将向科学界提供基因组数据。

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.