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.