Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/222664
Gene expression imputation provides clinical and biological insights into treatment-resistant schizophrenia polygenic risk
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
Genome-wide association studies (GWAS) have revealed the polygenic nature of treatment-resistant schizophrenia TRS. Gene expression imputation allowed the translation of GWAS results into regulatory mechanisms and the construction of gene expression (GReX) risk scores (GReX-RS). In the present study we computed GReX-RS from the largest GWAS of TRS to assess its association with clinical features. We perform transcriptome imputation in the largest GWAS of TRS to find GReX associated with TRS using brain tissues. Then, for each tissue, we constructed a GReX-RS of the identified genes in a sample of 254 genotyped first episode of psychosis (FEP) patients to test its association with clinical phenotypes, including clinical symptomatology, global functioning and cognitive performance. Our analysis provides evidence that the polygenic basis of TRS includes genetic variants that modulate the expression of certain genes in certain brain areas (substantia nigra, hippocampus, amygdala and frontal cortex), which at the same time are related to clinical features in FEP patients, mainly persistence of negative symptoms and cognitive alterations in sustained attention, which have also been suggested as clinical predictors of TRS. Our results provide a clinical explanation of the polygenic architecture of TRS and give more insight into the biological mechanisms underlying TRS.
Matèries
Matèries (anglès)
Citació
Citació
PROHENS COLL, Llucia, RODRÍGUEZ FERRET, Natalia, GONZÀLEZ SEGURA, Àlex, MARTÍNEZ PINTEÑO, Albert, OLIVARES BERJAGA, David, MARTÍNEZ-SERRANO, Irene, GONZÁLEZ, Aitor, MEZQUIDA MATEOS, Gisela, PARELLADA, Mara, CUESTA, Manuel j., BERNARDO ARROYO, Miquel, GASSÓ ASTORGA, Patricia, MAS HERRERO, Sergi. Gene expression imputation provides clinical and biological insights into treatment-resistant schizophrenia polygenic risk. _Psychiatry Research_. 2024. Vol. 332. [consulta: 7 de gener de 2026]. ISSN: 0165-1781. [Disponible a: https://hdl.handle.net/2445/222664]