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Do nuclear-encoded core subunits of mitochondrial complex I confer genetic susceptibility to schizophrenia in Han Chinese populations?

机译:线粒体复合体I的核编码核心亚单位是否赋予汉族人群精神分裂症遗传易感性?

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摘要

Schizophrenia is one of the most prevalent psychiatric disorders with complex genetic etiology. Accumulating evidence suggests that energy metabolism and oxidative stress play important roles in the pathophysiology of schizophrenia. Dysfunction of mitochondrial respiratory chain and altered expression of complex I subunits were frequently reported in schizophrenia. To investigate whether nuclear-encoded core subunit genes of mitochondrial complex I are associated with schizophrenia, we performed a genetic association study in Han Chinese. In total, 46 tag single nucleotide polymorphisms (SNPs) from 7 nuclear-encoded core genes of mitochondrial complex I were genotyped in 918 schizophrenia patients and 1042 healthy controls. We also analyzed these SNPs in a large sample mainly composed of Europeans through using the available GWAS datasets from the Psychiatric Genomics Consortium (PGC). No significant associations were detected between these SNPs and schizophrenia in Han Chinese and the PGC data set. However, we observed nominal significant associations of 2 SNPs in the NDUFS1 gene and 4 SNPs in the NDUFS2 gene with early onset schizophrenia (EOS), but none of these associations survived the Bonferroni correction. Taken together, our results suggested that common SNPs in the nuclear-encoded core subunit genes of mitochondrial complex I may not confer genetic susceptibility to schizophrenia.
机译:精神分裂症是遗传病因最复杂的精神疾病之一。越来越多的证据表明,能量代谢和氧化应激在精神分裂症的病理生理中起重要作用。精神分裂症中经常报道线粒体呼吸链功能异常和复杂的I亚基表达改变。为了研究线粒体复合体I的核编码核心亚基基因是否与精神分裂症相关,我们在汉族人群中进行了遗传关联研究。总共在918名精神分裂症患者和1042名健康对照中对来自线粒体复合体I的7个核编码核心基因的46个标签单核苷酸多态性(SNP)进行了基因分型。我们还使用来自精神病基因组学协会(PGC)的可用GWAS数据集,在主要由欧洲人组成的大样本中分析了这些SNP。在汉族人和PGC数据集之间未发现这些SNP与精神分裂症之间有显着关联。但是,我们观察到NDUFS1基因中的2个SNP和NDUFS2基因中的4个SNP与早期发作的精神分裂症(EOS)的名义显着显着关联,但是这些关联都没有幸免于Bonferroni矫正。综上所述,我们的结果表明,线粒体复合体I的核编码核心亚基基因中的常见SNP可能不会赋予精神分裂症遗传易感性。

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