Bipolar disorder (BPD) is a major public health priority, responsible for a vast burden of disability, personal suffering, and economic cost. Genetic susceptibility is the strongest known risk factor for BPD, and the identification of specific susceptibility genes would have enormous implications for advancing our understanding of the biology of BPD and revealing novel targets for treatment. The limited success to date of genetic studies of BPD has been due to its complex genetic architecture that likely includes many contributing loci of modest effect. Advances in population genetics and genotyping technologies have recently made the genetic dissection of complex disorders like BPD a feasible project. Genomewide association studies (GWAS) have already identified susceptibility variants underlying a range of other common medical disorders. However, it has become clear that much larger samples than are currently available will be needed to achieve such successes for BPD. This application is a response by an international consortium of investigators to RFA-MH-08-130: "Genomic Parsing of Bipolar Disorder and Schizophrenia: Studies of Large Cohorts in the U.S. and Across the Globe." The proposed International Cohort Collection for Bipolar Disorder (ICCBD) will address the need for large-scale DNA and data resources by establishing a uniquely large collection of samples and data from individuals with BPD.
The specific aims of this application are 1) to ascertain and collect a large cohort of BPD cases (N = 9000) and unaffected controls (N = 9000) over five years at two U.S. sites (Boston and Los Angeles) using novel high-throughput phenotyping methods;and 2) to construct a harmonized data resource for genetic studies combining phenotypic data from the U.S. case-control sample with a parallel, separately funded European case-control sample (10,000 cases and 10,000 controls) obtained from the UK and Sweden. Separately funded genotyping and genetic analyses of these resources will fully characterize common polymorphisms and copy number variants in the full sample to detect novel risk variants and attempt replication of the most compelling prior findings. This resource, augmented by existing samples, will provide an unprecedented platform for the discovery of the genetic determinants of BPD. Bipolar disorder (BPD) is a major public health priority, responsible for a vast burden of disability, personal suffering, and economic cost. Genetic susceptibility is the strongest known risk factor for BPD, and the identification of specific susceptibility genes would have enormous implications for advancing our understanding of the biology of BPD and revealing novel targets for treatment. The limited success to date of genetic studies of BPD has been due to its complex genetic architecture that likely includes many contributing loci of modest effect. The proposed International Cohort Collection for Bipolar Disorder (ICCBD) will address the need for large-scale DNA and data resources by establishing a uniquely large collection of samples and data from individuals with BPD.

Public Health Relevance

Bipolar disorder (BPD) is a major public health priority, responsible for a vast burden of disability, personal suffering, and economic cost. Genetic susceptibility is the strongest known risk factor for BPD, and the identification of specific susceptibility genes would have enormous implications for advancing our understanding of the biology of BPD and revealing novel targets for treatment. The limited success to date of genetic studies of BPD has been due to its complex genetic architecture that likely includes many contributing loci of modest effect. The proposed International Cohort Collection for Bipolar Disorder (ICCBD) will address the need for large-scale DNA and data resources by establishing a uniquely large collection of samples and data from individuals with BPD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH085542-05
Application #
8298183
Study Section
Special Emphasis Panel (ZMH1-ERB-S (07))
Program Officer
Addington, Anjene M
Project Start
2008-09-30
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2012
Total Cost
$1,961,599
Indirect Cost
$357,157
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Hartz, Sarah M; Bierut, Laura J; Pato, Michele T (2014) In reply. JAMA Psychiatry 71:969
Hartz, Sarah M; Pato, Carlos N; Medeiros, Helena et al. (2014) Comorbidity of severe psychotic disorders with measures of substance use. JAMA Psychiatry 71:248-54
Perlis, R H; Iosifescu, D V; Castro, V M et al. (2012) Using electronic medical records to enable large-scale studies in psychiatry: treatment resistant depression as a model. Psychol Med 42:41-50
Tatonetti, N P; Denny, J C; Murphy, S N et al. (2011) Detecting drug interactions from adverse-event reports: interaction between paroxetine and pravastatin increases blood glucose levels. Clin Pharmacol Ther 90:133-42
Hall, Mei-Hua; Smoller, Jordan W (2010) A new role for endophenotypes in the GWAS era: functional characterization of risk variants. Harv Rev Psychiatry 18:67-74