DLG2 rs11607886 polymorphism associated with schizophrenia and precuneus functional changes

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Schizophrenia (SZ) is a complex mental disorder with a significant genetic component.
• The DLG2 gene, encoding a postsynaptic scaffolding protein, has been implicated in SZ risk.
• The precise role of DLG2 genetic variations in SZ pathogenesis and brain function remains unclear.

Purpose of the Study:

• To investigate the association between DLG2 gene polymorphisms and schizophrenia susceptibility.
• To explore the relationship between DLG2 variations, altered brain function, and clinical symptoms in SZ patients.

Main Methods:

• Genotyping of single nucleotide polymorphisms (SNPs) rs11607886 and rs7479949 in 350 SZ patients and 407 healthy controls.
• Functional magnetic resonance imaging (fMRI) analysis of brain activity (ALFF, ReHo, FC) in specific genotype groups.
• Correlation of brain imaging data with clinical symptom assessments in SZ patients.

Main Results:

• The DLG2 rs11607886 polymorphism was significantly associated with schizophrenia.
• Significant differences in brain activity (ALFF, ReHo) were observed in the left precuneus gyrus (PCu).
• Altered functional connectivity (FC) between the left PCu and right middle temporal gyrus was found in SZ patients carrying the risk allele, correlating with cognitive deficits.

Conclusions:

• The rs11607886 polymorphism in DLG2 may contribute to schizophrenia pathogenesis.
• DLG2 is a potential candidate gene for schizophrenia, influencing cognitive function.
• The precuneus (PCu) plays a crucial role in schizophrenia, modulated by DLG2 genetic variations.