Dataset Information

Database of genetic studies of bipolar disorder.

ABSTRACT: This study describes the construction and preliminary analysis of a database of summary level genetic findings for bipolar disorder from the literature. The database is available for noncommercial use at http://bioprogramming.bsd.uchicago.edu/BDStudies/. This may be the first complete collection of published gene-specific linkage and association findings on bipolar disorder, including genome-wide association studies. Both the positive and negative findings have been incorporated so that the statistical and contextual significance of each finding may be compared semi-quantitatively and qualitatively across studies of mixed technologies. The database is appropriate for searching a literature populated by mainly underpowered studies, and if 'hits' are viewed as tentative knowledge for future hypothesis generation. It can serve as the basis for a mega-analysis of candidate genes. Herein, we discuss the most robust and best replicated gene findings to date in a contextual manner.

SUBMITTER: Piletz JE

PROVIDER: S-EPMC3134528 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Database of genetic studies of bipolar disorder.

Piletz John E JE Zhang Xiaotong X Ranade Rajdeep R Liu Chunyu C

Psychiatric genetics 20110401 2

This study describes the construction and preliminary analysis of a database of summary level genetic findings for bipolar disorder from the literature. The database is available for noncommercial use at http://bioprogramming.bsd.uchicago.edu/BDStudies/. This may be the first complete collection of published gene-specific linkage and association findings on bipolar disorder, including genome-wide association studies. Both the positive and negative findings have been incorporated so that the stat ...[more]

PMID: 21085053

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Project description:Bipolar disorder (BPD) is a debilitating heritable psychiatric disorder. Contemporary models for the manic pole of BPD have primarily utilized either single locus transgenics or treatment with psychostimulants. Our lab recently characterized a mouse strain, termed Madison (MSN), which naturally displays a manic phenotype, exhibiting elevated locomotor activity, increased sexual behavior, and higher forced swimming relative to control strains. Lithium chloride and olanzapine treatments attenuate this phenotype. In this study, we replicated our locomotor activity experiment, showing that MSN mice display generationally-stable mania relative to their outbred ancestral strain, hsd:ICR (ICR). We then performed a gene expression microarray experiment to compare hippocampus of MSN and ICR mice. We found dysregulation of multiple transcripts whose human orthologs are associated with BPD and other psychiatric disorders including schizophrenia and ADHD, including: Epor, Smarca4, Cmklr1, Cat, Tac1, Npsr1, Fhit, and P2rx7. RT-qPCR confirmed dysregulation for all of seven transcripts tested. Using a network analysis, we found dysregulation of a gene system related to chromatin packaging, a result convergent with recent human findings on BPD. Using a novel genomic enrichment algorithm, we found enrichment in genome regions homologous to human loci implicated in BPD in replicated linkage studies including homologs of human cytobands 1p36, 3p14, 3q29, 6p21-22, 12q24, 16q24, and 17q25. Our findings suggest that MSN mice represent a polygenic model for the manic pole of BPD showing much of the genetic systems complexity of the corresponding human disorder. Further, the high degree of convergence between our findings and the human literature on BPD brings up novel questions about evolution by analogy in mammalian genomes. In total, 12 total RNA samples were used for microarray analysis: 6 samples from Madison mice and 6 samples from ICR outbred mice. All samples were biological replicates.

Dataset Information

Database of genetic studies of bipolar disorder.

Publications

Database of genetic studies of bipolar disorder.

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