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均匀的人群中收集2500名双相情感障碍（BP）患者的大型队列的申请。对这些患者进行广泛的表型分析，包括用于双相情感障碍纵向评估的生命图表；对于选择性群体活动测量和脑成像数据（MRI）将获得。除了采集血液进行DNA和RNA提取外，所有受试者将被同意参加NIMH人类遗传学计划，以产生淋巴母细胞样细胞系，并向科学界提供。我们还将收集BP先证者的父母和兄弟姐妹的DNA，用于后续的遗传研究。由于神经精神特征的遗传易感基因的鉴定需要非常大的样本量，荷兰正在提出一个BP患者的国家登记册，其中有8000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。该应用补充了正在进行的nimh资助的精神分裂症全基因组关联研究（GWAS），该研究是由加州大学洛杉矶分校和UMC乌得勒支大学（荷兰）的同一个研究小组共同努力的。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提供了一个独特的机会来进行两种表型的比较分析，这将反过来促进重叠和独特的候选遗传易感性因素的识别。GWAS将使用收集到的先证物和已经可用的荷兰对照（1万至10万）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的荟萃分析的内部努力充分结合，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. 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.