Gene co-expression architecture in peripheral blood in a cohort of remitted first-episode schizophrenia patients.
Natalia RodriguezPatricia GassóAlbert Martínez-PinteñoÀlex-González SeguraGisela MezquidaLucia Moreno-IzcoJavier González-PeñasIñaki ZorrillaMarta MartinRoberto Rodriguez-JimenezIluminada CorripioSalvador SarróAngela IbáñezAnna ButjosaFernando ContrerasMiquel BioqueManuel-Jesús CuestaMara ParelladaAna González-PintoEsther BerrocosoMiguel BernardoSergi Masnull nullPublished in: Schizophrenia (Heidelberg, Germany) (2022)
A better understanding of schizophrenia subtypes is necessary to stratify the patients according to clinical attributes. To explore the genomic architecture of schizophrenia symptomatology, we analyzed blood co-expression modules and their association with clinical data from patients in remission after a first episode of schizophrenia. In total, 91 participants of the 2EPS project were included. Gene expression was assessed using the Clariom S Human Array. Weighted-gene co-expression network analysis (WGCNA) was applied to identify modules of co-expressed genes and to test its correlation with global functioning, clinical symptomatology, and premorbid adjustment. Among the 25 modules identified, six modules were significantly correlated with clinical data. These modules could be clustered in two groups according to their correlation with clinical data. Hub genes in each group showing overlap with risk genes for schizophrenia were enriched in biological processes related to metabolic processes, regulation of gene expression, cellular localization and protein transport, immune processes, and neurotrophin pathways. Our results indicate that modules with significant associations with clinical data showed overlap with gene sets previously identified in differential gene-expression analysis in brain, indicating that peripheral tissues could reveal pathogenic mechanisms. Hub genes involved in these modules revealed multiple signaling pathways previously related to schizophrenia, which may represent the complex interplay in the pathological mechanisms behind the disease. These genes could represent potential targets for the development of peripheral biomarkers underlying illness traits in clinical remission stages after a first episode of schizophrenia.
Keyphrases
- network analysis
- genome wide
- gene expression
- bipolar disorder
- end stage renal disease
- genome wide identification
- ejection fraction
- dna methylation
- newly diagnosed
- chronic kidney disease
- poor prognosis
- electronic health record
- peritoneal dialysis
- peripheral blood
- computed tomography
- bioinformatics analysis
- brain injury
- multiple sclerosis
- cell proliferation
- oxidative stress
- rheumatoid arthritis
- deep learning
- genome wide analysis
- amino acid
- endoplasmic reticulum stress
- data analysis
- mass spectrometry
- quality improvement
- human health
- drug induced
- pluripotent stem cells
- induced apoptosis