Transcriptome Analysis of Post-Mortem Brain Tissue Reveals Up-Regulation of the Complement Cascade in a Subgroup of Schizophrenia Patients
Autor: | Mitra Etemadikhah, Grazyna Rajkowska, Craig A. Stockmeier, Lars Feuk, Adnan Niazi, Eva Lindholm Carlström, Bo Nilsson, Jonatan Halvardson, Stefan Enroth |
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Rok vydání: | 2021 |
Předmět: |
Adult
Male QH426-470 Biology Bioinformatics complement cascade Article Transcriptome 03 medical and health sciences brain tissue 0302 clinical medicine Gene expression Genetics medicine Humans Prefrontal cortex Gene Genetics (clinical) 030304 developmental biology Aged 0303 health sciences Gene Expression Profiling C4A Neurosciences Complement System Proteins Middle Aged medicine.disease 3. Good health Complement system Up-Regulation schizophrenia Gene Ontology Schizophrenia Postmortem Changes Orbitofrontal cortex Female transcriptome 030217 neurology & neurosurgery Neurovetenskaper |
Zdroj: | Genes Volume 12 Issue 8 Genes, Vol 12, Iss 1242, p 1242 (2021) |
ISSN: | 2073-4425 |
Popis: | Schizophrenia is a genetically complex neuropsychiatric disorder with largely unresolved mechanisms of pathology. Identification of genes and pathways associated with schizophrenia is important for understanding the development, progression and treatment of schizophrenia. In this study, pathways associated with schizophrenia were explored at the level of gene expression. The study included post-mortem brain tissue samples from 68 schizophrenia patients and 44 age and sex-matched control subjects. Whole transcriptome poly-A selected paired-end RNA sequencing was performed on tissue from the prefrontal cortex and orbitofrontal cortex. RNA expression differences were detected between case and control individuals, focusing both on single genes and pathways. The results were validated with RT-qPCR. Significant differential expression between patient and controls groups was found for 71 genes. Gene ontology analysis of differentially expressed genes revealed an up-regulation of multiple genes in immune response among the patients (corrected p-value = 0.004). Several genes in the category belong to the complement system, including C1R, C1S, C7, FCN3, SERPING1, C4A and CFI. The increased complement expression is primarily driven by a subgroup of patients with increased expression of immune/inflammatory response genes, pointing to important differences in disease etiology within the patient group. Weighted gene co-expression network analysis highlighted networks associated with both synaptic transmission and activation of the immune response. Our results demonstrate the importance of immune-related pathways in schizophrenia and provide evidence for elevated expression of the complement cascade as an important pathway in schizophrenia pathology. |
Databáze: | OpenAIRE |
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