Decreased CNNM2 expression in prefrontal cortex affects sensorimotor gating function, cognition, dendritic spine morphogenesis and risk of schizophrenia.
Neuropsychopharmacology
; 49(2): 433-442, 2024 Jan.
Article
in En
| MEDLINE
| ID: mdl-37715107
ABSTRACT
Genome-wide association studies (GWASs) have reported multiple single nucleotide polymorphisms (SNPs) associated with schizophrenia, yet the underlying molecular mechanisms are largely unknown. In this study, we aimed to identify schizophrenia relevant genes showing alterations in mRNA and protein expression associated with risk SNPs at the 10q24.32-33 GWAS locus. We carried out the quantitative trait loci (QTL) and summary data-based Mendelian randomization (SMR) analyses, using the PsychENCODE dorsolateral prefrontal cortex (DLPFC) expression QTL (eQTL) database, as well as the ROSMAP and Banner DLPFC protein QTL (pQTL) datasets. The gene CNNM2 (encoding a magnesium transporter) at 10q24.32-33 was identified to be a robust schizophrenia risk gene, and was highly expressed in human neurons according to single cell RNA-seq (scRNA-seq) data. We further revealed that reduced Cnnm2 in the mPFC of mice led to impaired cognition and compromised sensorimotor gating function, and decreased Cnnm2 in primary cortical neurons altered dendritic spine morphogenesis, confirming the link between CNNM2 and endophenotypes of schizophrenia. Proteomics analyses showed that reduced Cnnm2 level changed expression of proteins associated with neuronal structure and function. Together, these results identify a robust gene in the pathogenesis of schizophrenia.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Schizophrenia
/
Cation Transport Proteins
Type of study:
Clinical_trials
/
Etiology_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Neuropsychopharmacology
Journal subject:
NEUROLOGIA
/
PSICOFARMACOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China