Co-expression modules construction by WGCNA and identify potential hub genes and regulation pathways of postpartum depression.

Zhifang Deng ,Jue Liu ,Jie Tu ,Aiping Deng ,Yuan Yang ,Cheng Yuan ,Wei Cai ,Han Xiao ,Wenqi Gao

doi:10.52586/5006

Abstract

Purpose: The purpose of our present study was to, for the first time, identify key genes associated with postpartum depression (PPD) and discovery the potential molecular mechanisms of this condition. Methods: First, microarray expression profiles GSE45603 dataset were acquired from the Gene Expression Omnibus (GEO) in National Center for Biotechnology Information (NCBI). The weighted gene co-expression network analysis (WGCNA) was performed to identify the top three modules from differentially expressed genes (DEGs). Furthermore, cross-validated differential gene expression analysis of the top three modules and DEGs was used to identify the hub genes. Gene set enrichment analysis (GSEA) was conducted to identify the potential functions of the hub genes. We conducted a Receiver Operator Characteristic (ROC) curve to verify the diagnostic efficiencies of the hub genes. Lastly, GSE44132 dataset was used to search the association between the methylation profiles of the hub genes and susceptibility to PPD. Results: Altogether, 8979 genes were identified as DEGs for WGCNA analysis. The turquoise, yellow, and green functional modules were the most significant modules related to PPD development after WGCNA analysis. The enrichment analysis results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway demonstrated that hub genes in the three modules were mainly enriched in the neurotrophin signaling pathway, chemokine signaling pathway, Fcγ receptor-mediated phagocytosis, and Mitogen-activated protein kinase (MAPK) signaling pathway. Eight genes (HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, SPI1) were identified as "real" hub genes from cross-validation data of the three modules and DEGs, and possessed diagnostic value in PPD. The GSEA suggested that "OLFACTORY_TRANSDUCTION", "BUTANOATE_METABOLISM", "MELANOMA", "AMINOACYL_TRNA_BIOSYNTHESIS", and "LYSINE_DEGRADATION" were all crucial in the development of PPD. Highly significant differentially methylated positions in the three genes (HNRNPA2B1, RPL13A and UBA52) were identified in the GSE44132. Conclusion: Using WGCNA analysis of GEO data, our present study, for the first time, may contribute to elucidate the pathophysiology of PPD and provide potential diagnostic biomarkers and therapeutic targets for postpartum depression.

Highlights

Postpartum depression (PPD) is one of the most prominent mood disorders affecting 15% of parturient women [1]
As for biological pathway (BP), the upregulated differentially expressed genes (DEGs) were mainly implicated in the regulation of translation, rRNA processing, regulation of immune response, and SRP-dependent cotranslational protein targeting the membrane
Our results found that, compared with healthy control, HNRNPA2B1 was down-regulated and ribosomal protein L13a (RPL13A) and UBA52 were up-regulated in the PPD samples, respectively (Fig. 5A), we considered that lowly expression of HNRNPA2B1 and highly expressions of RPL13A and UBA52 were involved in which pathways

Summary

Introduction

Postpartum depression (PPD) is one of the most prominent mood disorders affecting 15% of parturient women [1]. PPD may result in both short-term and long-term negative effects on neonatal and infant development, cognition, emotion, and behavior. Previous studies have shown that maternal depression is a risk factor for higher rates of premature and low-birth-weight babies, infant malnutrition and stunting, and infant diarrhoeal, which can lead to mothers’ reluctance to care for their children and impair normal mother-child relationships. PPD is the result of the combined influence of multiple factors. Previous studies have reported hypotheses regarding the physiopathologic mechanisms of PPD, such as the abnormal changes of hormones, neurotransmitters, inflammatory factors [4], among others. There is no exact evidence to support any of the above conclusions, and the physiopathologic mechanisms of PPD remain largely obscure

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