Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes
Schizophrenia is a complex neurodevelopmental disorder with high rate of morbidity and mortality. While the heritability rate is high, the precise etiology is still unknown. Although schizophrenia is a central nervous system disorder, studies using peripheral tissues have also been established to se...
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Uppsala universitet, Medicinsk genetik och genomik
2020
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ftuppsalauniv:oai:DiVA.org:uu-421855 2023-05-15T17:44:47+02:00 Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes Etemadikhah, Mitra Niazi, Adnan Wetterberg, Lennart Feuk, Lars 2020 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-421855 https://doi.org/10.1038/s41598-020-57467-z eng eng Uppsala universitet, Medicinsk genetik och genomik Uppsala universitet, Science for Life Laboratory, SciLifeLab Uppsala universitet, Beräkningsbiologi och bioinformatik Karolinska Inst, Dept Clin Neurosci CNS, K8, Stockholm, Sweden. Springer Nature Scientific Reports, 2020, 10:1, orcid:0000-0003-0311-5279 orcid:0000-0003-2355-2919 http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-421855 doi:10.1038/s41598-020-57467-z PMID 31959813 ISI:000562133800003 info:eu-repo/semantics/openAccess Psychiatry Psykiatri Article in journal info:eu-repo/semantics/article text 2020 ftuppsalauniv https://doi.org/10.1038/s41598-020-57467-z 2023-02-23T22:00:34Z Schizophrenia is a complex neurodevelopmental disorder with high rate of morbidity and mortality. While the heritability rate is high, the precise etiology is still unknown. Although schizophrenia is a central nervous system disorder, studies using peripheral tissues have also been established to search for patient specific biomarkers and to increase understanding of schizophrenia etiology. Among all peripheral tissues, fibroblasts stand out as they are easy to obtain and culture. Furthermore, they keep genetic stability for long period and exhibit molecular similarities to cells from nervous system. Using a unique set of fibroblast samples from a genetically isolated population in northern Sweden, we performed whole transcriptome sequencing to compare differentially expressed genes in seven controls and nine patients. We found differential fibroblast expression between cases and controls for 48 genes, including eight genes previously implicated in schizophrenia or schizophrenia related pathways; HGF, PRRT2, EGR1, EGR3, C11orf87, TLR3, PLEKHH2 and PIK3CD. Weighted gene correlation network analysis identified three differentially co-expressed networks of genes significantly-associated with schizophrenia. All three modules were significantly suppressed in patients compared to control, with one module highly enriched in genes involved in synaptic plasticity, behavior and synaptic transmission. In conclusion, our results support the use of fibroblasts for identification of differentially expressed genes in schizophrenia and highlight dysregulation of synaptic networks as an important mechanism in schizophrenia. Article in Journal/Newspaper Northern Sweden Uppsala University: Publications (DiVA) Scientific Reports 10 1 |
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Uppsala University: Publications (DiVA) |
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ftuppsalauniv |
language |
English |
topic |
Psychiatry Psykiatri |
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Psychiatry Psykiatri Etemadikhah, Mitra Niazi, Adnan Wetterberg, Lennart Feuk, Lars Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes |
topic_facet |
Psychiatry Psykiatri |
description |
Schizophrenia is a complex neurodevelopmental disorder with high rate of morbidity and mortality. While the heritability rate is high, the precise etiology is still unknown. Although schizophrenia is a central nervous system disorder, studies using peripheral tissues have also been established to search for patient specific biomarkers and to increase understanding of schizophrenia etiology. Among all peripheral tissues, fibroblasts stand out as they are easy to obtain and culture. Furthermore, they keep genetic stability for long period and exhibit molecular similarities to cells from nervous system. Using a unique set of fibroblast samples from a genetically isolated population in northern Sweden, we performed whole transcriptome sequencing to compare differentially expressed genes in seven controls and nine patients. We found differential fibroblast expression between cases and controls for 48 genes, including eight genes previously implicated in schizophrenia or schizophrenia related pathways; HGF, PRRT2, EGR1, EGR3, C11orf87, TLR3, PLEKHH2 and PIK3CD. Weighted gene correlation network analysis identified three differentially co-expressed networks of genes significantly-associated with schizophrenia. All three modules were significantly suppressed in patients compared to control, with one module highly enriched in genes involved in synaptic plasticity, behavior and synaptic transmission. In conclusion, our results support the use of fibroblasts for identification of differentially expressed genes in schizophrenia and highlight dysregulation of synaptic networks as an important mechanism in schizophrenia. |
format |
Article in Journal/Newspaper |
author |
Etemadikhah, Mitra Niazi, Adnan Wetterberg, Lennart Feuk, Lars |
author_facet |
Etemadikhah, Mitra Niazi, Adnan Wetterberg, Lennart Feuk, Lars |
author_sort |
Etemadikhah, Mitra |
title |
Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes |
title_short |
Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes |
title_full |
Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes |
title_fullStr |
Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes |
title_full_unstemmed |
Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes |
title_sort |
transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes |
publisher |
Uppsala universitet, Medicinsk genetik och genomik |
publishDate |
2020 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-421855 https://doi.org/10.1038/s41598-020-57467-z |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Scientific Reports, 2020, 10:1, orcid:0000-0003-0311-5279 orcid:0000-0003-2355-2919 http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-421855 doi:10.1038/s41598-020-57467-z PMID 31959813 ISI:000562133800003 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1038/s41598-020-57467-z |
container_title |
Scientific Reports |
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10 |
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1 |
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1766147066556317696 |