Since 1988 the NIMH Genetics Initiative has supported a national resource for the study of bipolar disorder (BP). This extension of the national genetic resource will include a sample of 5000 unrelated BP probands and 2000 parents for case-control, and family-based association studies. Control samples will be obtained through the NIMH Genetics Initiative national resource. Probands and parents will be ascertained and assessed at eleven sites (the ten sites previously participating plus Howard University, which will provide African-American probands). Parental DNAs in a subsample will allow control for ethnic stratification. This sample will be a national resource for fine scale linkage disequilibrium mapping within regions of linkage, as well as genetic association studies.? ? Previously, we carried out the first genome-wide genetic association study of bipolar disorder, using over 550,000 single nucleotide markers and cases drawn from this collection, as well as controls collected by the NIMH Genetics Initiative, along with a set of cases and controls collected by collaborators in Germany. ? ? A major related project, known as the Bipolar Disorder Phenome Project, aims to collate all of the clinical data collected from all 4000+ participants in the Genetics Initiative study that have been enrolled since 1992. This database was completed released to the scientific community in 2007.? ? Last year, this sample was selected by the Genetic Association Information Network (GAIN)for genotyping using 1 million single nucleotide markers. The genotyping was completed in early 2008 and the data have been released to the scientific community as a resource for genetic studies. ? ? A large group of collaborators is analyzing these data. We are focusing on genes that play a role in shaping the clinical picture of bipolar disorder, and response to treatment. We are testing the idea that subtypes of bipolar disorder, defined by differing clinical features, will prove to be a more tractable target for genetic association studies, producing larger effects that can be more easily replicated in independent samples. Key clinical features in this project include polarity at onset, frequency of manic and depressive episodes, and global functioning. We are also exploring variables that might be used to estimate an individual's response to lithium, one of the most effective current treatments for bipolar disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH002842-05
Application #
7735177
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2008
Total Cost
$547,363
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
McMahon, Francis J (2016) Genetic association studies in psychiatry: time for pay-off. Lancet Psychiatry 3:309-10
Ross, Jessica; Berrettini, Wade; Coryell, William et al. (2008) Genome-wide parametric linkage analyses of 644 bipolar pedigrees suggest susceptibility loci at chromosomes 16 and 20. Psychiatr Genet 18:191-8
Baum, A E; Akula, N; Cabanero, M et al. (2008) A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry 13:197-207
Potash, James B; Buervenich, Silvia; Cox, Nancy J et al. (2008) Gene-based SNP mapping of a psychotic bipolar affective disorder linkage region on 22q12.3: association with HMG2L1 and TOM1. Am J Med Genet B Neuropsychiatr Genet 147B:59-67
Detera-Wadleigh, Sevilla D; Liu, Chun-yu; Maheshwari, Manjula et al. (2007) Sequence variation in DOCK9 and heterogeneity in bipolar disorder. Psychiatr Genet 17:274-86
Lopez, Victor A; Detera-Wadleigh, Sevilla; Cardona, Imer et al. (2007) Nested association between genetic variation in tryptophan hydroxylase II, bipolar affective disorder, and suicide attempts. Biol Psychiatry 61:181-6
McMahon, Francis J (2007) A success at the end of an era, and a glimpse of things to come. Am J Psychiatry 164:999-1001
Goes, Fernando S; Zandi, Peter P; Miao, Kuangyi et al. (2007) Mood-incongruent psychotic features in bipolar disorder: familial aggregation and suggestive linkage to 2p11-q14 and 13q21-33. Am J Psychiatry 164:236-47
Potash, James B; Toolan, Jennifer; Steele, Jo et al. (2007) The bipolar disorder phenome database: a resource for genetic studies. Am J Psychiatry 164:1229-37
Xu, W; Schulze, T G; DePaulo, J R et al. (2006) A tree-based model for allele-sharing-based linkage analysis in human complex diseases. Genet Epidemiol 30:155-69

Showing the most recent 10 out of 19 publications