RT Journal Article
T1 Gene expression imputation provides clinical and biological insights into treatment-resistant schizophrenia polygenic risk
A1 Prohens, Llucia
A1 Parellada Redondo, María José
A1 Mas, Sergi
AB 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.
PB Elsevier
SN 0165-1781
YR 2024
FD 2024-01-03
LK https://hdl.handle.net/20.500.14352/119880
UL https://hdl.handle.net/20.500.14352/119880
LA eng
NO Prohens L, Rodríguez N, Segura ÀG, Martínez-Pinteño A, Olivares-Berjaga D, Martínez I, González A, Mezquida G, Parellada M, Cuesta MJ, Bernardo M, Gassó P, Mas S. Gene expression imputation provides clinical and biological insights into treatment-resistant schizophrenia polygenic risk. Psychiatry Res. 2024 Feb;332:115722. doi: 10.1016/j.psychres.2024.115722. Epub 2024 Jan 5. PMID: 38198858.
NO Instituto de Salud Carlos III
NO Unión Europea
NO Gobierno de Cataluña
DS Docta Complutense
RD 25 dic 2025