Systematic review of genome-wide gene expression studies of bipolar disorder

BMC Psychiatry

Research Article

Fernando S Goes¹  Jennifer T Judy¹  Mehdi Pirooznia¹  Fayaz Seifuddin¹  Peter P Zandi²  James B Potash³ 

[1] Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA;Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA;Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA;Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA;

关键词: Microarray;    Gene expression;    Bipolar disorder;    Mega-analysis;    FKBP5;    WFS1;    Genome-wide;    Brain;    Prefrontal cortex;    Hippocampus;   

DOI  :  10.1186/1471-244X-13-213

 received in 2013-05-02, accepted in 2013-08-13,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundNumerous genome-wide gene expression studies of bipolar disorder (BP) have been carried out. These studies are heterogeneous, underpowered and use overlapping samples. We conducted a systematic review of these studies to synthesize the current findings.MethodsWe identified all genome-wide gene expression studies on BP in humans. We then carried out a quantitative mega-analysis of studies done with post-mortem brain tissue. We obtained raw data from each study and used standardized procedures to process and analyze the data. We then combined the data and conducted three separate mega-analyses on samples from 1) any region of the brain (9 studies); 2) the prefrontal cortex (PFC) (6 studies); and 3) the hippocampus (2 studies). To minimize heterogeneity across studies, we focused primarily on the most numerous, recent and comprehensive studies.ResultsA total of 30 genome-wide gene expression studies of BP done with blood or brain tissue were identified. We included 10 studies with data on 211 microarrays on 57 unique BP cases and 229 microarrays on 60 unique controls in the quantitative mega-analysis. A total of 382 genes were identified as significantly differentially expressed by the three analyses. Eleven genes survived correction for multiple testing with a q-value < 0.05 in the PFC. Among these were FKBP5 and WFS1, which have been previously implicated in mood disorders. Pathway analyses suggested a role for metallothionein proteins, MAP Kinase phosphotases, and neuropeptides.ConclusionWe provided an up-to-date summary of results from gene expression studies of the brain in BP. Our analyses focused on the highest quality data available and provided results by brain region so that similarities and differences can be examined relative to disease status. The results are available for closer inspection on-line at Metamoodics [http://metamoodics.igm.jhmi.edu/], where investigators can look up any genes of interest and view the current results in their genomic context and in relation to leading findings from other genomic experiments in bipolar disorder.

【 授权许可】

Unknown   
© Seifuddin et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.