Transcriptome Analysis of Post-Mortem Brain Tissue Reveals Up-Regulation of the Complement Cascade in a Subgroup of Schizophrenia Patients

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 ass...

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Vydáno v:Genes Ročník 12; číslo 8; s. 1242
Hlavní autoři: Lindholm Carlström, Eva, Niazi, Adnan, Etemadikhah, Mitra, Halvardson, Jonatan, Enroth, Stefan, Stockmeier, Craig A., Rajkowska, Grazyna, Nilsson, Bo, Feuk, Lars
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland MDPI AG 13.08.2021
MDPI
Témata:
Adult
Aged
Autopsy
brain tissue
complement
Complement activation
complement cascade
Complement component C1r
Complement component C1s
Complement System Proteins - metabolism
Etiology
Female
Gene expression
Gene Expression Profiling
gene expression regulation
Gene Ontology
Gene regulation
genes
Genomes
Humans
Immune response
Immune system
Inflammation
Male
Medical research
Mental disorders
Middle Aged
Patients
Postmortem Changes
Prefrontal cortex
RNA
Schizophrenia
Schizophrenia - genetics
Schizophrenia - metabolism
Schizophrenia - pathology
Synaptic transmission
transcriptome
Transcriptomes
transcriptomics
Up-Regulation
Values
United States > US
Germany
brain tissue
schizophrenia
transcriptome
complement cascade
ISSN:2073-4425, 2073-4425
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Shrnutí: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.
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These authors contributed equally to this work.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes12081242