Abstract
Major depressive disorder (MDD) is a leading cause of disability worldwide, although its etiology and mechanism remain unknown. The aim of our study was to identify hub genes associated with MDD and to illustrate the underlying mechanisms. A weighted gene co-expression network analysis (WGCNA) was performed to identify significant gene modules and hub genes associated with MDD in peripheral blood mononuclear cells (PBMCs) (n = 45). In the blue module (R 2 = 0.95), five common hub genes in both co-expression network and protein–protein interaction (PPI) network were regarded as “real” hub genes. In another independent dataset, GSE52790, four genes were still significantly down-regulated in PBMCs from MDD patients compared with the controls. Furthermore, these four genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in PBMCs from 33 MDD patients and 41 healthy controls. The qRT-PCR analysis showed that ATP synthase membrane subunit c locus 1 (ATP5G1) was significantly down-regulated in samples from MDD patients than in control samples (t = −2.89, p-value = 0.005). Moreover, this gene was significantly differentially expressed between patients and controls in the prefrontal cortex (z = −2.83, p-value = 0.005). Highly significant differentially methylated positions were identified in the Brodmann area 25 (BA25), with probes in the ATP5G1 gene being significantly associated with MDD: cg25495775 (t = 2.82, p-value = 0.008), cg25856120 (t = −2.23, p-value = 0.033), and cg23708347 (t = −2.24, p-value = 0.032). These findings indicate that the ATP5G1 gene is associated with the pathogenesis of MDD and that it could serve as a peripheral biomarker for MDD.
Highlights
Major depressive disorder (MDD), a common mental disorder with a lifetime prevalence of around 15% in the general population (Tsai, 2006), is predicted to become the second leading cause of disability-adjusted life years in 2020 (Murray and Lopez, 1997)
In the GSE52790 dataset, four genes were still significantly down-regulated in the MDD group compared with the control group
The RT-Quantitative Real-Time PCR (qPCR) analysis results indicated that ATP5G1 was significantly down-regulated in samples from MDD patients compared with the control samples (t = −2.89, p-value = 0.005)
Summary
Major depressive disorder (MDD), a common mental disorder with a lifetime prevalence of around 15% in the general population (Tsai, 2006), is predicted to become the second leading cause of disability-adjusted life years in 2020 (Murray and Lopez, 1997). Some evidence has demonstrated that transcriptional alterations in peripheral blood mononuclear cells (PBMCs) may reflect the molecular changes in the brain (Fisar and Raboch, 2008; Fan et al, 2015). Rollins et al found that PBMCs and the brain may share a common mRNA expression pattern (Rollins et al, 2010). The central nervous system may affect the gene expression of peripheral lymphocytes via neurotransmitters, cytokines, or hormones, which may explain the comparable gene expression levels between peripheral blood and some brain tissues (Gladkevich et al, 2004). Several studies have found that the aberrant expression of mRNAs in PBMC samples might be involved in the pathogenesis of MDD (Rocc et al, 2002; Lee and Kim, 2010).
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.