International Journal of Clinical Research

Objective: To analyze and screen functional single nucleotide polymorphisms related to the pathogenesis of schizophrenia by bioinformatics methods, and to explore the relationship between functional susceptibility site polymorphisms and the pathogenesis of schizophrenia and its brain imaging changes. Methods: Schizophrenia data sets were downloaded from dbgap database and psychiatric genomics alliance. The candidate genes and gene pathways overlapped in different data sets were analyzed by enrichment analysis. A total of 540 schizophrenic patients and 540 controls were included from January 2016 to January 2020. Genomic DNA was extracted from the blood of all subjects, and the resting brain MRI data of 40 cases and 40 controls were collected. GWAS based on mixed pool was used to select 4 overlapping gene pathways as the research object. 28 single nucleotides including 4 pathways were genotyped by direct iplex mass spectrometry. Taking the obtained positive sites as the grouping standard, the case-control subjects with imaging data were divided into different subgroups according to genotyping, and the differences of brain imaging between different subgroups were studied, To explore the relationship between positive susceptibility genes and brain imaging changes. Results: the European and American schizophrenia data set and the mixed pool GWAS analysis of this study found that the abnormalities of vascular smooth muscle contraction, calcium signaling pathway and cell adhesion molecule may be related to the pathogenesis of schizophrenia, and the allele of rs12101060( χ2 = 4.852, P = 0.029) and genotype (χ2 = 4.796, P = 0.029). Allele A was a risk variant (or = 7.317, 95% CI: 0.911-58.779). Allele of rs12966547 (χ2 = 8.824, P = 0.003) and genotype (χ2 = 11.484, P = 0.003). The G mutation of rs12966547 was a risk factor for SCZ (or = 1.537, 95% CI: 1.157-2.043). All SNPs with statistical significance were located in genes with regulatory function, including the allele of rs12101060, the interaction between disease status in the right orbital frontal gyrus and the a + genotype at rs12101060. Conclusion: the abnormal regulation of biological processes caused by single nucleotide polymorphisms may be the cause of schizophrenia. The polymorphisms of rs12101060 and rs12966547 are related to the pathogenesis of schizophrenia in China. The right orbital frontal gyrus may be the brain region with a + genotype specific changes at rs12101060.

Schizophrenia; Single-Nucleotide Polymorphisms; GESA; fMRI; Brain Function