University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Schizophr Bull. 2010 Sep;36(5):983-90. doi: 10.1093/schbul/sbp002. Epub 2009 Mar 12.
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 of RGS4 variants 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). RGS4 polymorphisms are associated with variations in cognitive functions and contribute a small but statistically significant proportion of variance in a family-based sample.
RGS4 基因编码调节 G 蛋白信号转导亚基 4 的多态性可能与精神分裂症有关。在首发精神分裂症患者中，它们也与背外侧前额叶皮层（DLPFC）体积有关。DLPFC 是调节与精神分裂症发病机制相关的可遗传认知功能的关键区域。为了进一步了解 RGS4 变体与精神分裂症的关系，我们研究了它们与精神分裂症患者及其亲属认知功能的关系。我们分析了 31 个基于 2 个受影响一级亲属的多基因、多代白种人精神分裂症家系。所有参与者都接受了计算机化神经认知测试，该测试评估了抽象/心理灵活性、注意力、言语、空间和面部记忆以及空间能力的准确性和速度（反应时间）。对代表常见多态性的“标签”单核苷酸多态性（SNP）进行了基因分型。使用连锁分析序列进行了考虑到家庭关系的测量基因型分析。SNP rs10917670（“SNP1”）和 rs951439（“SNP7”）与面部记忆速度（P=0.0003）相关，在经过 Bonferroni 校正（P=0.039）的显著水平下仍然存在。这些相同的 SNP 之前曾被报道与精神分裂症有关。SNP rs10917670（“SNP1”）和 rs951439（“SNP7”）与面部记忆效率（P=0.03）和言语记忆效率（P=0.02）、rs28757217 与抽象/心理灵活性速度（P=0.02）和言语记忆效率（P=0.03）、SNP18（rs2661319）与空间记忆准确性（P=0.02）和面部记忆速度（P=0.03）也存在未校正的关联。RGS4 多态性与认知功能的变化有关，并在基于家庭的样本中对小但具有统计学意义的变异比例有贡献。
