DLG2 rs11607886多态性与精神分裂症和楔前叶功能改变相关

IF 3.6 2区医学 Q1 PSYCHIATRY

Schizophrenia Research Pub Date : 2025-04-13 DOI:10.1016/j.schres.2025.04.004

HanYu Zhu , Zhaoyang Wu , Junxiao Wang , Enhui Zhang , Sen Zhang , Yongfeng Yang , Wenqiang Li , Han Shi , Ge Yang , Luxian Lv , Yan Zhang

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引用次数: 0

摘要

背景与假设精神分裂症（schizophrenia， SZ）是一种具有高度遗传性的严重精神障碍。DLG2编码突触后支架蛋白DLG2 (PSD93，突触后密度蛋白93)，其变异与SZ风险增加相关。然而，DLG2基因座变异在SZ中的作用尚不清楚。本研究旨在探讨DLG2基因多态性与SZ易感性的关系，以及DLG2与SZ患者脑功能改变和临床症状的关系。研究设计对350例SZ患者和407例健康对照（hc）的单核苷酸多态性rs11607886和rs7479949进行基因分型。将47例SZ患者和79例hc分型为两组：风险A等位基因携带者组和gg纯组。进一步分析功能磁共振成像（fMRI）指标。随后，将不同脑区的数据与临床症状评估相关联。研究结果dlg2 rs11607886与SZ显著相关。在ALFF和ReHo中发现了显著的主要影响，特别是对左侧楔前叶回（PCu）。基因型与诊断之间存在显著的交互作用，对FC有显著影响，携带SZ等位基因A的患者的FC在左PCu和右颞中回之间增加（r = - 0.336， punp校正= 0.042），与空间宽度得分呈负相关（r = 0.444， pfdr校正= 0.002）。结论DLG2基因rs11607886多态性可能影响SZ的发病机制，并对认知功能有潜在影响。本研究强调DLG2是SZ的候选基因，PCu在SZ中起重要作用。

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DLG2 rs11607886 polymorphism associated with schizophrenia and precuneus functional changes

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, P_un-corrected = 0.042) and negatively correlated with spatial breadth scores (r = 0.444, P_{FDR-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.

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来源期刊

Schizophrenia Research 医学-精神病学

CiteScore

7.50

自引率

8.90%

发文量

429

审稿时长

10.2 weeks

期刊介绍： As official journal of the Schizophrenia International Research Society (SIRS) Schizophrenia Research is THE journal of choice for international researchers and clinicians to share their work with the global schizophrenia research community. More than 6000 institutes have online or print (or both) access to this journal - the largest specialist journal in the field, with the largest readership! Schizophrenia Research''s time to first decision is as fast as 6 weeks and its publishing speed is as fast as 4 weeks until online publication (corrected proof/Article in Press) after acceptance and 14 weeks from acceptance until publication in a printed issue. The journal publishes novel papers that really contribute to understanding the biology and treatment of schizophrenic disorders; Schizophrenia Research brings together biological, clinical and psychological research in order to stimulate the synthesis of findings from all disciplines involved in improving patient outcomes in schizophrenia.