Luan Zhilin, Lu Tianlan, Ruan Yanyan, Yue Weihua, Zhang Dai
Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, China.
The Sixth Hospital and Institute of Mental Health, Peking University, Beijing, 100191, China.
Neurosci Bull. 2016 Jun;32(3):239-45. doi: 10.1007/s12264-016-0026-9. Epub 2016 Apr 8.
It has been suggested that altered neurogenesis may be involved in the etiology of schizophrenia, so genes impacting on neurogenesis could be potential candidates for schizophrenia. A member of the Musashi family, the human MSI2 gene plays a substantial role in stem-cell maintenance, asymmetric division, and differentiation during neurogenesis. Our previous genome-wide association study (GWAS) implied an association of MSI2 with schizophrenia in a Han Chinese population. To further explore this association, three single-nucleotide polymorphisms (SNPs), rs9892791, rs11657292, and rs1822381, were selected for a replication study involving 921 schizophrenia cases and 1244 controls. After rigorous Bonferroni correction, two of the SNPs (rs9892791 and rs11657292) displayed significant differences in allele and genotype distribution frequencies between the case and control groups. When our GWAS and replication samples were combined, the three MSI2 SNPs were all strongly associated with schizophrenia (rs9892791: allelic P = 1.07E-5; rs11657292: allelic P = 1.95E-12; rs1822381: allelic P = 1.44E-4). These results indicate that the human MSI2 gene might be a susceptibility gene for schizophrenia and encourage future research on the functional relationship between this gene and schizophrenia.
有人提出，神经发生改变可能与精神分裂症的病因有关，因此影响神经发生的基因可能是精神分裂症的潜在候选基因。人类MSI2基因是Musashi家族的一员，在神经发生过程中的干细胞维持、不对称分裂和分化中起重要作用。我们之前的全基因组关联研究（GWAS）表明，在汉族人群中MSI2与精神分裂症有关联。为了进一步探究这种关联，我们选择了三个单核苷酸多态性（SNP），即rs9892791、rs11657292和rs1822381，进行一项涉及921例精神分裂症患者和1244名对照的重复研究。经过严格的Bonferroni校正后，其中两个SNP（rs9892791和rs11657292）在病例组和对照组之间的等位基因和基因型分布频率上显示出显著差异。当我们将GWAS样本和重复研究样本合并后，这三个MSI2 SNP均与精神分裂症强烈相关（rs9892791：等位基因P = 1.07E - 5；rs11657292：等位基因P = 1.95E - 12；rs1822381：等位基因P = 1.44E - 4）。这些结果表明，人类MSI2基因可能是精神分裂症的一个易感基因，并鼓励未来对该基因与精神分裂症之间的功能关系进行研究。
