RGS4 polymorphisms associated with variability of cognitive performance in a family-based schizophrenia sample.
RGS4 polymorphisms associated with variability of cognitive performance in a family-based schizophrenia sample.
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RGS4 多态性与基于家庭的精神分裂症样本中认知表现的变异性相关。
DOI：
10.1093/schbul/sbp002
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发表时间：
2010
影响因子：
6.6
通讯作者：
Nimgaonkar,VishwajitL
中科院分区：
文献类型：
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作者：
Prasad,KonasaleM;Almasy,Laura;Gur,RubenC;Gur,RaquelE;Pogue-Geile,Michael;Chowdari,KodavaliV;Talkowski,MichaelE;Nimgaonkar,VishwajitL
编码G蛋白信号调节子4亚型（RGS 4）的基因多态性可能与精神分裂症相关。在首发精神分裂症患者中，它们还与背外侧前额叶皮质（DLPFC）体积相关。DLPFC是调节精神分裂症发病机制中涉及的遗传性认知功能的关键区域。为了进一步了解RGS 4变异与精神分裂症的关系，我们在精神分裂症患者及其亲属中研究了它们与认知功能的关系。我们分析了31个多重，多代高加索家庭与精神分裂症招募的基础上，2个受影响的一级亲属。所有参与者都接受了计算机化神经认知电池，评估了抽象/心理灵活性的准确性和速度（反应时间）;注意力;言语，空间和面部记忆;和空间能力。对代表常见多态性的“标签”单核苷酸多态性（SNP）进行基因分型。使用顺序寡基因连锁分析程序进行了考虑家庭关系的测量基因型分析。SNPs rs 10917670（“SNP 1”）和rs 951439（“SNP 7”）与面部记忆速度（P= 0.0003）在Bonferroni校正后（P= 0.039）的显著性水平上相关。同样的SNPs早先也被报道与精神分裂症有关。rs 10917670（“SNP 1”）和rs 951439（“SNP 7”）与面孔记忆效率也存在未校正的关联（P= 0.03）和非文字记忆效率（P= 0.02），rs 28757217在抽象/心理灵活性速度上（P= 0.02）和非文字记忆效率（P= .03），SNP18（rs 2661319）空间记忆准确性（P= 0.02）和面孔记忆速度（P= .03）。RGS 4多态性与认知功能的变化相关，并且在以家庭为基础的样本中贡献了一小部分但具有统计学意义的变异。
Polymorphisms of the gene encoding the regulator of G protein signaling, subtype 4 (RGS4), may be associated with schizophrenia. Among first-episode schizophrenia patients, they are also associated with dorsolateral prefrontal cortex (DLPFC) volume. The DLPFC is a key region that regulates heritable cognitive functions implicated in schizophrenia pathogenesis. To further understand the relationship ofRGS4variants to schizophrenia, we examined their associations with cognitive functions among schizophrenia patients and their relatives. We analyzed 31 multiplex, multigenerational Caucasian families with schizophrenia recruited on the basis of 2 affected first-degree relatives. All participants underwent a computerized neurocognitive battery that evaluates accuracy and speed (response time) of performance on abstraction/mental flexibility; attention; verbal, spatial, and face memory; and spatial ability. “Tag” single-nucleotide polymorphisms (SNPs) representing common polymorphisms were genotyped. Measured genotype analyses accounting for family relationships were performed using Sequential Oligogenic Linkage Analysis Routines. SNPs rs10917670 (“SNP1”) and rs951439 (“SNP7”) were associated with face memory speed (P= .0003) at a significance level that survived Bonferroni correction (P= .039). The same SNPs have earlier been reported to be associated with schizophrenia. There also were uncorrected associations with rs10917670 (“SNP1”) and rs951439 (“SNP7”) on face memory efficiency (P= .03) and verbal memory efficiency (P= 0.02), rs28757217 on abstraction/mental flexibility speed (P= .02) and verbal memory efficiency (P= .03), SNP18 (rs2661319) on spatial memory accuracy (P= 0.02) and face memory speed (P= .03).RGS4polymorphisms are associated with variations in cognitive functions and contribute a small but statistically significant proportion of variance in a family-based sample.