Evaluation of the Genetics of Bipolar Disorder

Study Description: This project uses genetic mapping and whole exome sequencing methods to identify genetic markers and variations that contribute to the risk of bipolar disorder, an often severe, heritable condition affecting about one percent of the population. Individuals diagnosed with bipolar disorder are studied, along with their relatives. Phenotypic information obtained from clinical interviews and family history is correlated with genotypic information obtained from genetic marker and whole exome sequencing methods. Objectives: Primary Objective: Identify genes involved in bipolar disorder and related conditions so that better methods of diagnosis, treatment, and prevention can be developed. Secondary Objectives: 1. To identify genes that shape the clinical picture or influence response to treatment. 2. To replicate our findings in independent samples. Genome-wide genotyping, whole exome sequencing, demographic, and phenotype data will be requested under the usual dbGaP Data Access procedures and analyzed along with existing phenotypic and genetic data. 3. To analyze the clinical data, including but not limited to the diagnostic categories, in order to identify between-family differences which might identify genetically meaningful subgroups of families. 4. To submit coded phenotypes, genotypes, and DNA from informative families to a national archival database. 5. To establish a catalog of induced pluripotent stem cells suitable for functional genomic studies of neurons and glia in culture. Endpoints: Primary Endpoint: The primary endpoint of this study is the identification of genes involved in risk for developing bipolar disorder. Secondary Endpoints: 1. Pedigree structure, representing known relationships and reported mental health of first, second, and third-degree relatives 2. Dimensional data on mental health symptoms obtained from the Past History Schedule, Mood Disorders Questionnaire, and Symptom Checklist (SCL-90) 3. Cognitive data based on measures of executive function, working memory, attention, verbal memory, visuospatial reasoning, and affect recognition. 4. Lithium response data collected through the Retrospective Assessment of the Lithium Response (Alda) Scale 5. History of traumatic life events elicited with the Life Events Checklist for DSM-5 (LEC-5) 6. Genotype data obtained from SNP arrays or whole-exome sequencing 7. Skin biopsy or additional blood sample from selected participants 8. Induced pluripotent stem cells obtained from reprogramming of skin or blood cells.