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| Status |
Public on Jan 08, 2014 |
| Title |
RNA-sequencing of the brain transcriptome implicates dysregulation of neuroplasticity, circadian rhythms, and GTPase binding in bipolar disorder |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
See "Akula et al., Molecular Psychiatry in Press". RNA-sequencing (RNA-seq) is a powerful technique to investigate the complexity of gene expression in the human brain. We used RNA-seq to survey the brain transcriptome in high-quality post-mortem dorsolateral prefrontal cortex from 11 individuals diagnosed with bipolar disorder (BD) and from 11 age- and gender-matched controls. Deep sequencing was performed, with over 350 million reads per specimen. At a false-discovery rate of <5%, we detected 5 differentially-expressed (DE) genes and 12 DE transcripts, most of which have not been previously implicated in BD. Among these, PROM1/CD133 and ABCG2 play important roles in neuroplasticity. We also show for the first time differential expression of long non-coding RNAs (lncRNAs) in BD. DE transcripts include those of SRSF5 and RFX4, which along with lncRNAs play a role in mammalian circadian rhythms. The DE genes were significantly enriched for several Gene Ontology (GO) categories. Of these, genes involved with GTPase binding were also enriched for BD-associated SNPs from previous genome-wide association studies, suggesting that differential expression of these genes is not simply a consequence of BD or its treatment. Many of these findings were replicated by microarray in an independent sample of 60 cases and controls. These results highlight common pathways for inherited and non-inherited influences on disease risk that may constitute good targets for novel therapies.
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| Overall design |
Brain transcriptome in bipolar disorder
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| Contributor(s) |
Akula N, McMahon FJ |
| Citation(s) |
24393808 |
| Submission date |
Dec 11, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Nirmala Akula |
| E-mail(s) |
akulan@mail.nih.gov
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| Organization name |
National Institute of Mental Health/National Institutes of Health
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| Department |
Human Genetics Branch
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| Street address |
Building 35, Room 1A-205
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| City |
Bethesda |
| State/province |
Maryland |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (2) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
| GPL15433 |
Illumina HiSeq 1000 (Homo sapiens) |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA231202 |
| SRA |
SRP033725 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE53239_HGB1-10_geneLevel_HTSeqCountData.txt.gz |
445.6 Kb |
(ftp)(http) |
TXT |
| GSE53239_HGB1-10_transcriptLevel_eXpressCountData.txt.gz |
5.2 Mb |
(ftp)(http) |
TXT |
| GSE53239_HGB11-22_geneLevel_HTSeqCountData.txt.gz |
579.6 Kb |
(ftp)(http) |
TXT |
| GSE53239_HGB11-22_transcriptLevel_eXpressCountData.txt.gz |
6.6 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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