Common variants in MAGI2 gene are associated with increased risk for cognitive impairment in schizophrenic patients.
Common variants in MAGI2 gene are associated with increased risk for cognitive impairment in schizophrenic patients.
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DOI：
10.1371/journal.pone.0036836
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ozaki N
中科院分区：
文献类型：
--
作者：
Koide T;Banno M;Aleksic B;Yamashita S;Kikuchi T;Kohmura K;Adachi Y;Kawano N;Kushima I;Nakamura Y;Okada T;Ikeda M;Ohi K;Yasuda Y;Hashimoto R;Inada T;Ujike H;Iidaka T;Suzuki M;Takeda M;Iwata N;Ozaki N
精神分裂症是一种以阳性症状、阴性症状和认知障碍为特征的复杂精神障碍。MAGI2是一个相对较大的基因（约1.5 Mbps），定位于染色体7q21，参与神经递质受体的募集，如AMPA-和nmda型谷氨酸受体。一项旨在评估MAGI2与认知表现或精神分裂症之间关系的遗传关联研究尚未进行。在这项病例对照研究中，我们在大量日本样本中检测了MAGI2单核苷酸多态性（SNP）变异与精神分裂症风险的关系，并探索了MAGI2变异与谷氨酸活性相关的人类认知功能方面之间的潜在关系。基于首次在日本人群中进行的精神分裂症全基因组关联研究（JGWAS）的结果，我们选择了4个独立的snp，并使用一个大型的日本独立样本集（病例1624，对照1621）进行了关联研究。采用威斯康辛卡片分类测验（WCST）评价114例患者和91例对照组的执行功能。我们在日本人群中发现了MAGI2位点内常见snp与精神分裂症遗传关联的证据。此外，在MAGI2与认知表现的相关性方面，我们发现rs2190665基因型对WCST评分有显著影响（p = 0.034）， rs4729938基因型有显著影响（p = 0.08）。总之，尽管我们没有发现强有力的遗传证据表明日本人群中常见的MAGI2变异与精神分裂症风险增加有关，但这些snp可能会增加精神分裂症患者认知障碍的风险。
Schizophrenia is a complex psychiatric disorder characterized by positive symptoms, negative symptoms, and cognitive impairment. MAGI2, a relatively large gene (∼1.5 Mbps) that maps to chromosome 7q21, is involved in recruitment of neurotransmitter receptors such as AMPA- and NMDA-type glutamate receptors. A genetic association study designed to evaluate the association between MAGI2 and cognitive performance or schizophrenia has not been conducted. In this case-control study, we examined the relationship of single nucleotide polymorphism (SNP) variations in MAGI2 and risk for schizophrenia in a large Japanese sample and explored the potential relationships between variations in MAGI2 and aspects of human cognitive function related to glutamate activity. Based on the result of first schizophrenia genome-wide association study in a Japanese population (JGWAS), we selected four independent SNPs and performed an association study using a large independent Japanese sample set (cases 1624, controls 1621). Wisconsin Card Sorting Test (WCST) was used to evaluate executive function in 114 cases and 91 controls. We found suggestive evidence for genetic association of common SNPs within MAGI2 locus and schizophrenia in Japanese population. Furthermore in terms of association between MAGI2 and cognitive performance, we observed that genotype effect of rs2190665 on WCST score was significant (p = 0.034) and rs4729938 trended toward significance (p = 0.08). In conclusion, although we could not detect strong genetic evidence for association of common variants in MAGI2 and increased schizophrenia risk in a Japanese population, these SNPs may increase risk of cognitive impairment in schizophrenic patients.
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影响因子：
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作者：
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通讯作者：
Green, Michael F.
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稀有变体会产生整个基因组的关联。
影响因子：
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作者：
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通讯作者：
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