Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds.
Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds.
复制标题
与精神分裂症相关的基因和电生理测度的分析揭示了Znf804a与新声音引起的P300B振幅的关联。
DOI：
10.1038/tp.2013.117
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发表时间：
2014-01-14
影响因子：
6.8
通讯作者：
Petryshen TL
中科院分区：
文献类型：
--
作者：
Del Re EC;Bergen SE;Mesholam-Gately RI;Niznikiewicz MA;Goldstein JM;Woo TU;Shenton ME;Seidman LJ;McCarley RW;Petryshen TL
近年来，通过全基因组关联研究（GWAS）发现了几个与精神分裂症（SZ）相关的基因，其中ZNF 804 A被认为在转录调控中起作用。然而，这些基因赋予的下游病理生理变化仍有待阐明。143例受试者（68例临床高危、首次发作或慢性病例; 75例对照），我们检查了先前由SZ GWAS鉴定的或与SZ的假定中间表型相关的21个遗传标记物与三种事件相关电位（ERP）测量之间的关联：失匹配负波（MMN）、听觉古怪任务期间的P300振幅和听觉新奇古怪任务期间的P300振幅。在控制年龄和性别的情况下，ZNF 804 A标记rs 1344706与由新声音引起的P300振幅之间检测到了超过Bonferroni校正的显著遗传关联（beta=4.38，P=1.03 × 10−4），这被认为是对意外的显著刺激的注意定向的指标。随后的分析显示，这种关联是由对照受试者驱动的（β =6.35，P=9.08 × 10−5），并且风险等位基因与较高的新P300 b振幅相关，而在病例中观察到的振幅显著低于对照组。新的P300 b振幅显着相关的神经认知措施的听觉注意干扰条件下，表明新的P300 b振幅和高阶注意过程之间的关系。我们的研究结果表明，多效性的影响ZNF 804 A的风险SZ和神经机制，索引的新的P300 b ERP组件。
Several genes have recently been identified as risk factors for schizophrenia (SZ) by genome-wide association studies (GWAS), including ZNF804A which is thought to function in transcriptional regulation. However, the downstream pathophysiological changes that these genes confer remain to be elucidated. In 143 subjects (68 clinical high risk, first episode or chronic cases; 75 controls), we examined the association between 21 genetic markers previously identified by SZ GWAS or associated with putative intermediate phenotypes of SZ against three event-related potential (ERP) measures: mismatch negativity (MMN), amplitude of P300 during an auditory oddball task, and P300 amplitude during an auditory novelty oddball task. Controlling for age and sex, significant genetic association surpassing Bonferroni correction was detected between ZNF804A marker rs1344706 and P300 amplitude elicited by novel sounds (beta=4.38, P=1.03 × 10−4), which is thought to index orienting of attention to unexpected, salient stimuli. Subsequent analyses revealed that the association was driven by the control subjects (beta=6.35, P=9.08 × 10−5), and that the risk allele was correlated with higher novel P300b amplitude, in contrast to the significantly lower amplitude observed in cases compared to controls. Novel P300b amplitude was significantly correlated with a neurocognitive measure of auditory attention under interference conditions, suggesting a relationship between novel P300b amplitude and higher-order attentional processes. Our results suggest pleiotropic effects of ZNF804A on risk for SZ and neural mechanisms that are indexed by the novel P300b ERP component.
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