Polymorphism screening and association analysis of the plexin/semaphorin genes in neuropsychiatric diseases

根据精神分裂症病因学的神经发育假说，神经丛/信号素基因可能参与了该病的发病机制。我们基于NCBI数据库中的数据库搜索了这些基因在Silico中的非同义多态。检测到的基因多态与神经精神疾病进行关联分析。在一系列研究中，我们发现Sema3d的Lys701Gln多态与精神分裂症有显著关联，我们对506名精神分裂症患者和941名健康对照组的样本进行了基因分型。Gln701等位基因对精神分裂症的发生有显著的保护作用(p=0.0069)。此外，不包括Lys701G1n变异的单倍型rs2190208-rs1029564-rs17159614-rs121176601与精神分裂症相关(p=0.00001)，这表明Sema3d的其他一些多态在精神分裂症的发病中起作用。我们的发现提供了强有力的证据，表明Sema3d增加了精神分裂症的易感性，这可能导致这种疾病的神经发育障碍。

Based on the neurodevelopmental hypothesis in the etiology of schizophrenia, the plexin/semaphorin genes might be involved in the pathogenesis of the illness. We searched for non-synonymous polymorphisms of these genes in silico based on the NCBI dbSNP database. Detected polymorphisms were subject to association analyses with neuropsychiatric diseases. In a series of studies, we found a significant association between the Lys701Gln polymorphism of SEMA3D and schizophrenia, genotyping a sample of 506 patients with schizophrenia and 941 healthy control subjects. The Gln701 allele showed a significant protective effect against the development of schizophrenia (p=0.0069). In addition, the haplotype rs2190208-rs1029564-rs17159614-rs121176601, not including the Lys701G1n variant, was shown to be associated with schizophrenia (p=0.00001), which suggests that some other polymorphisms of SEMA3D play a role in the pathogenesis of schizophrenia. Our findings provide strong evidence that SEMA3D confers susceptibility to schizophrenia, which could contribute to the neurodevelopmental impairments in the disorder.