1Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China
2The Sixth Hospital and Institute of Mental Health, Peking University, Beijing 100191, China
3Key Laboratory of Mental Health, Ministry of Health and National Clinical Research Center for Mental Disorders (Peking University), Beijing 100191, China

Abstract 

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.

Keywords

Schizophrenia, Neurogenesis, Single-nucleotide polymorphism, Musashi, MSI2

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