The Human MSI2 Gene is Associated with Schizophrenia in the Chinese Han Population

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: MSI2; Musashi; Neurogenesis; Schizophrenia; Single-nucleotide polymorphism.

Fig. 1

Genomic structure and linkage disequilibrium (LD) of MSI2. A Genomic structure of the human MSI2 gene. The gene spans 423 kb, and the largest isoform is composed of 11 exons. The positions of the three SNPs selected for the replication study are indicated by arrowheads. B LD of the MSI2 gene in a previous GWAS. Pairwise LDs were computed for all possible combinations of the 229 SNPs using D′ values. The number in each cell represents the D′ value after the decimal point between SNPs. The three SNPs are in three different LD blocks shown in the grey panel and magnified in the upper panel.