Schizophrenia research · 2025
DLG2 rs11607886 polymorphism associated with schizophrenia and precuneus functional changes.
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Zhu HanYu, Wu Zhaoyang, Wang Junxiao, Zhang Enhui, Zhang Sen, Yang Yongfeng, Li Wenqiang, Shi Han, Yang Ge, Lv Luxian, Zhang Yan
Аннотация
BACKGROUND AND HYPOTHESIS: Schizophrenia (SZ) is a severe mental disorder with high heritability. DLG2 encodes the postsynaptic scaffolding protein DLG2 (PSD93, Postsynaptic Density Protein 93), and its variants were associated with an increased risk of SZ. However, the role of DLG2 locus variation in SZ remains elusive. This study aims to investigate the association between DLG2 gene polymorphisms and SZ susceptibility and the relationship between DLG2 and altered brain function and clinical symptoms in SZ patients.
STUDY DESIGN: Single nucleotide polymorphisms (SNPs) rs11607886 and rs7479949 were genotyped in 350 SZ patients and 407 healthy controls (HCs). 47 SZ patients and 79 HCs were genotyped into two groups: the risk A allele carrier group and the GG-pure group. Functional magnetic resonance imaging (fMRI) indices were further analyzed. Subsequently, data from different brain regions were correlated with clinical symptom assessment.
STUDY RESULTS: DLG2 rs11607886 was significantly associated with SZ. Significant main effects were found in the ALFF and ReHo, especially for the left precuneus gyrus (PCu). A significant interaction between genotype and diagnosis had a significant effect on FC, which was increased between the left PCu and the right middle temporal gyrus in carriers of the A allele with SZ (r = -0.336, Pun-corrected = 0.042) and negatively correlated with spatial breadth scores (r = 0.444, PFDR-corrected = 0.002).
CONCLUSIONS: The rs11607886 polymorphism in DLG2 may influence the pathogenesis of SZ and have potential effects on cognitive function. The present study emphasizes DLG2 as a candidate gene for SZ and suggests an important role for PCu in SZ.
STUDY DESIGN: Single nucleotide polymorphisms (SNPs) rs11607886 and rs7479949 were genotyped in 350 SZ patients and 407 healthy controls (HCs). 47 SZ patients and 79 HCs were genotyped into two groups: the risk A allele carrier group and the GG-pure group. Functional magnetic resonance imaging (fMRI) indices were further analyzed. Subsequently, data from different brain regions were correlated with clinical symptom assessment.
STUDY RESULTS: DLG2 rs11607886 was significantly associated with SZ. Significant main effects were found in the ALFF and ReHo, especially for the left precuneus gyrus (PCu). A significant interaction between genotype and diagnosis had a significant effect on FC, which was increased between the left PCu and the right middle temporal gyrus in carriers of the A allele with SZ (r = -0.336, Pun-corrected = 0.042) and negatively correlated with spatial breadth scores (r = 0.444, PFDR-corrected = 0.002).
CONCLUSIONS: The rs11607886 polymorphism in DLG2 may influence the pathogenesis of SZ and have potential effects on cognitive function. The present study emphasizes DLG2 as a candidate gene for SZ and suggests an important role for PCu in SZ.