Duan Zeng1, Shen He1, Changlin Ma2, Yi Wen2, Weichen Song3, Qingqing Xu1, Nan Zhao4, Qiang Wang4, Yimin Yu5, Yifeng Shen5, Jingjing Huang6, Huafang Li7. 1. Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. 2. Shanghai Jiading District Mental Health Center, Shanghai, PR China. 3. Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. Electronic address: smhcmict@163.com. 4. Department of Psychiatry, Shanghai Pudong New Area Mental Health Center, Tongji University School of Medicine, Shanghai, PR China. 5. Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Shanghai Clinical Research Center for Mental Health, Shanghai, PR China. 6. Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Shanghai Clinical Research Center for Mental Health, Shanghai, PR China. Electronic address: jjhuang_att@163.com. 7. Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Shanghai Clinical Research Center for Mental Health, Shanghai, PR China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai, PR China. Electronic address: lhlh_5@163.com.
Abstract
BACKGROUND: Suicide is a serious and global health problem that has a strong association with major depressive disorder (MDD). Weighted gene co-expression network analysis (WGCNA) was performed for the construction of a co-expression network to get important gene modules associated with depressed suicide. METHODS: Transcriptome sequencing data from dorsolateral prefrontal cortex was used, which included 29 non-psychiatric controls (CON), 21 MDD suicides (MDD-S) and 9 MDD non-suicides (MDD-NS) of medication-free sudden death individuals. RESULTS: The highest correlation in the module-traits relationship was discovered between the black module and suicide (r = -0.30, p = 0.024) as well as MDD (r = -0.34, p = 0.010).Furthermore, the expression levels of genes decreased progressively across the three groups (CON>MDD-NS>MDD-S). Therefore, the genes in the black module was selected for subsequent analyses. Protein-Protein Interaction Network found that the top 10 hub genes were somehow involved in depressed suicide including JUN, FOS, ATF3, MYC, EGR1, FOSB, DUSP1, NFKBIA, TLR2, NR4A1. Most of the GO terms were enriched in cell death and apoptosis and KEGG was mainly enriched in MAPK pathway. Cell Type-Specific Analysis found these genes were significantly enriched in endothelial and microglia (p<0.000) cell types. In addition, 92 genes in this module had at least one highly significant differentially methylated positions between MDD-S and controls. CONCLUSION: Cell death and apoptosis may participate in the interplay between depressed suicide and neuro-inflammation system.
BACKGROUND: Suicide is a serious and global health problem that has a strong association with major depressive disorder (MDD). Weighted gene co-expression network analysis (WGCNA) was performed for the construction of a co-expression network to get important gene modules associated with depressed suicide. METHODS: Transcriptome sequencing data from dorsolateral prefrontal cortex was used, which included 29 non-psychiatric controls (CON), 21 MDD suicides (MDD-S) and 9 MDD non-suicides (MDD-NS) of medication-free sudden death individuals. RESULTS: The highest correlation in the module-traits relationship was discovered between the black module and suicide (r = -0.30, p = 0.024) as well as MDD (r = -0.34, p = 0.010).Furthermore, the expression levels of genes decreased progressively across the three groups (CON>MDD-NS>MDD-S). Therefore, the genes in the black module was selected for subsequent analyses. Protein-Protein Interaction Network found that the top 10 hub genes were somehow involved in depressed suicide including JUN, FOS, ATF3, MYC, EGR1, FOSB, DUSP1, NFKBIA, TLR2, NR4A1. Most of the GO terms were enriched in cell death and apoptosis and KEGG was mainly enriched in MAPK pathway. Cell Type-Specific Analysis found these genes were significantly enriched in endothelial and microglia (p<0.000) cell types. In addition, 92 genes in this module had at least one highly significant differentially methylated positions between MDD-S and controls. CONCLUSION: Cell death and apoptosis may participate in the interplay between depressed suicide and neuro-inflammation system.
Authors: Ahmed B Alarabi; Attayeb Mohsen; Kenji Mizuguchi; Fatima Z Alshbool; Fadi T Khasawneh Journal: BMC Med Genomics Date: 2022-04-14 Impact factor: 3.622