Abstract
Background: Bipolar disorder (BP) is one of the most common mental illnesses, with the underlying mechanisms remaining unclear. The aim of this study is to investigate the novel genetic risk of BP by systematically reviewing published literature and performing a meta-analysis. Method: A comprehensive search of electronic databases was completed using Illumina BioEngine. RNA expression data from brain tissue of 198 BP cases and 160 controls were analyzed, including six BP case/control bio-sets from four recent studies. The selected top BP risk genes were analyzed by integrating an online open source BP genetic database. Pathway enrichment analysis (PEA) and network connectivity analysis (NCA) were conducted to identify potential functional association between target genes and BP. Results: Top three target genes were identified through the meta-analysis for BP, including MT1E, MT1X, and CX3CR1. These genes play roles within multiple BP genetic pathways and demonstrate solid connections with known BP target genes. NCA results also revealed a strong functional association between these genes and BP. Conclusion: This study identified well-studied and novel BP target genes and their functional pathways that influence the BP pathogenesis. Our results may provide new insights into the understanding of the genetic mechanisms of BP.
Highlights
Bipolar disorder (BP) is one of the most common mental illnesses, characterized by recurrent episodes of mania and depression which affect thought, perception, emotions, and social behavior
BDNF, RELN and ANK3 were suggested as potential biomarkers for the disease . [5,6,7] Jang et al found that the genetic dysfunction of Trpm2 causes uncontrolled phosphorylation of GSK-3, which may lead to the pathology of BP [8]
Our study identified novel BP risk genes and evaluated the effectiveness of integrating meta-analysis and Pathway Studio (PS) ResNet database to identify and evaluate novel BP risk genes
Summary
Bipolar disorder (BP) is one of the most common mental illnesses, characterized by recurrent episodes of mania and depression which affect thought, perception, emotions, and social behavior. The cause of BP remains unclear, it has been hypothesized that the genetic factors play important roles in the development of BP [1, 2]. The heritability study estimates for BP range between 60 % and 80 % [4]. These studies suggest a substantial involvement of genetic factors in the development of the disorder. Bipolar disorder (BP) is one of the most common mental illnesses, with the underlying mechanisms remaining unclear. The aim of this study is to investigate the novel genetic risk of BP by systematically reviewing published literature and performing a metaanalysis
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