The association between axon guidance pathway single nucleotide polymorphisms and susceptibility to schizophrenia / 中华行为医学与脑科学杂志

ABSTRACT

Objective To investigate the susceptibility related sites to schizophrenia through whole genome analysis combined with bioinformatics analysis method.Methods The research was carried out by two stages.In the first stage,300 cases of schizophrenia and 300 healthy controls were enrolled,and 5ml pe-ripheral venous blood was drawn to extract genome DNA.After quality control and concentration adjustment by ultraviolet spectrophotometer,equal mass of DNA was mixed into DNA pooling for case group and control group respectively.Genome-Wide Human SNP Array 6.0 chips were used to detect the polymorphism of the SNP.Plink software was used to locate the differential SNP to genes.GSEA was used to analyze the gene to pathway.Ten loci with the smallest P value of screened pathway were chosen as investigated subjects.In the second stage,240 schizophrenias and 200 healthy controls were collected to gain the genome DNA to verity the genotype of the 10 loci.Results Many single nucleotide polymorphism loci which P<9.2×10-8were found in GWAS.The GSEA pathway analysis showed that the axon guidance pathway was significantly related to the incidence of schizophrenia.The distribution of rs4632195 genotypes involved the distribution of among 10 loci(χ2=11.484,P=0.003)and alleles(χ2=8.824,P=0.009)were statistically significant,and T al-lele was susceptibility genes of schizophrenia(OR=1.537,95%CI1.157-2.203).Conclusion rs4632195 of DCC gene in the axon guidance pathway is associated with schizophrenia,and the T allele is associated with susceptibility to schizophrenia.