Transcriptome changes in relation to manic episode

Ya Chin Lee, Yu Lin Chao, Chiao Erh Chang, Ming Hsien Hsieh, Kuan Ting Liu, Hsi Chung Chen, Mong Liang Lu, Wen Yin Chen, Chun Hsin Chen, Mong Hsun Tsai, Tzu Pin Lu, Ming Chyi Huang, Po Hsiu Kuo

Research output: Contribution to journalArticle

Abstract

Bipolar disorder (BD) is highly heritable and well known for its recurrent manic and depressive episodes. The present study focused on manic episode in BD patients and aimed to investigate state-specific transcriptome alterations between acute episode and remission, including messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and micro-RNAs (miRNAs), using microarray and RNA sequencing (RNA-Seq) platforms. BD patients were enrolled with clinical information, and peripheral blood samples collected at both acute and remission status spanning for at least 2 months were confirmed by follow-ups. Symptom severity was assessed by Young Mania Rating Scale. We enrolled six BD patients as the discovery samples and used the Affymetrix Human Transcriptome Array 2.0 to capture transcriptome data at the two time points. For replication, expression data from Gene Expression Omnibus that consisted of 11 BD patients were downloaded, and we performed a mega-analysis for microarray data of 17 patients. Moreover, we conducted RNA sequencing (RNA-Seq) in additional samples of 7 BD patients. To identify intraindividual differentially expressed genes (DEGs), we analyzed data using a linear model controlling for symptom severity. We found that noncoding genes were of majority among the top DEGs in microarray data. The expression fold change of coding genes among DEGs showed moderate to high correlations (∼0.5) across platforms. A number of lncRNAs and two miRNAs (MIR181B1 and MIR103A1) exhibited high levels of gene expression in the manic state. For coding genes, we reported that the taste function-related genes, including TAS2R5 and TAS2R3, may be mania state-specific markers. Additionally, four genes showed a nominal p-value of less than 0.05 in all our microarray data, mega-analysis, and RNA-Seq analysis. They were upregulated in the manic state and consisted of MS4A14, PYHIN1, UTRN, and DMXL2, and their gene expression patterns were further validated by quantitative real-time polymerase chain reaction (PCR) (qRT-PCR). We also performed weight gene coexpression network analysis to identify gene modules for manic episode. Genes in the mania-related modules were different from the susceptible loci of BD obtained from genome-wide association studies, and biological pathways in relation to these modules were mainly related to immune function, especially cytokine-cytokine receptor interaction. Results of the present study elucidated potential molecular targets and genomic networks that are involved in manic episode. Future studies are needed to further validate these biomarkers for their roles in the etiology of bipolar illness.

Original languageEnglish
Article number280
JournalFrontiers in Psychiatry
Volume10
Issue numberMAY
DOIs
Publication statusPublished - Jan 1 2019

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Bipolar Disorder
Transcriptome
Genes
RNA Sequence Analysis
Long Noncoding RNA
Gene Regulatory Networks
MicroRNAs
Gene Expression
Cytokine Receptors
Genome-Wide Association Study
Microarray Analysis
Real-Time Polymerase Chain Reaction
Linear Models
Biomarkers
Cytokines
Weights and Measures
Messenger RNA

Keywords

  • Bipolar disorder
  • Manic episode
  • Microarray
  • Noncoding RNAs
  • RNA-sequencing
  • State markers
  • Transcriptome

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Lee, Y. C., Chao, Y. L., Chang, C. E., Hsieh, M. H., Liu, K. T., Chen, H. C., ... Kuo, P. H. (2019). Transcriptome changes in relation to manic episode. Frontiers in Psychiatry, 10(MAY), [280]. https://doi.org/10.3389/fpsyt.2019.00280

Transcriptome changes in relation to manic episode. / Lee, Ya Chin; Chao, Yu Lin; Chang, Chiao Erh; Hsieh, Ming Hsien; Liu, Kuan Ting; Chen, Hsi Chung; Lu, Mong Liang; Chen, Wen Yin; Chen, Chun Hsin; Tsai, Mong Hsun; Lu, Tzu Pin; Huang, Ming Chyi; Kuo, Po Hsiu.

In: Frontiers in Psychiatry, Vol. 10, No. MAY, 280, 01.01.2019.

Research output: Contribution to journalArticle

Lee, YC, Chao, YL, Chang, CE, Hsieh, MH, Liu, KT, Chen, HC, Lu, ML, Chen, WY, Chen, CH, Tsai, MH, Lu, TP, Huang, MC & Kuo, PH 2019, 'Transcriptome changes in relation to manic episode', Frontiers in Psychiatry, vol. 10, no. MAY, 280. https://doi.org/10.3389/fpsyt.2019.00280
Lee YC, Chao YL, Chang CE, Hsieh MH, Liu KT, Chen HC et al. Transcriptome changes in relation to manic episode. Frontiers in Psychiatry. 2019 Jan 1;10(MAY). 280. https://doi.org/10.3389/fpsyt.2019.00280
Lee, Ya Chin ; Chao, Yu Lin ; Chang, Chiao Erh ; Hsieh, Ming Hsien ; Liu, Kuan Ting ; Chen, Hsi Chung ; Lu, Mong Liang ; Chen, Wen Yin ; Chen, Chun Hsin ; Tsai, Mong Hsun ; Lu, Tzu Pin ; Huang, Ming Chyi ; Kuo, Po Hsiu. / Transcriptome changes in relation to manic episode. In: Frontiers in Psychiatry. 2019 ; Vol. 10, No. MAY.
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KW - Microarray

KW - Noncoding RNAs

KW - RNA-sequencing

KW - State markers

KW - Transcriptome

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