Analysis Of The Association Between GRIA1,GRM3,TCF4 Single Nucleotide Polymorphisms And Schizophrenia

Objective:Schizophrenia is a severe complex chronic psychiatric disorder with a heterogeneous clinical phenotype that affects about one percent of the world’s population.The disorder always suffers the youth,and brings heavy economical and social burdens to families and societies.After studying schizophrenia for a century,the cause of the disorder remains unknown.Years of studies have found that schizophrenia is a polygenic genetic disease,the accumulation of multiple micro-genes combined with environmental factors together lead to schizophrenia,and genetic factor plays pivotal roles in pathogenesis of schizophrenia.Therefore,investigating the susceptible genes is thus important for understanding,the genetic basis of schizophrenia.We tried to explore the susceptible genes of schizophrenia from the following strategies:First,exploring the association between GRIA1,GRM3 and schizophrenia in Han Chinese from Yunnan province by the glutamate pathway;Sencond,exploring the association between sensorimotor-gating-related TCF4 and schizophrenia in Han Chinese from Yunnan province based on the GWAS data.Methods:In this study,12 SNPs were genotyped by the SNaPshot assay.Deviation from the Hardy-Weinberg equilibrium(HWE),calculations and association tests for each SNP between the case and control groups were performed using the PLINK v1.07.Linkage disequilibrium(LD)structure was determined using the Haploview 4.2.The haplotype frequency was calculated using the SHEsis(http://analysis.bio-x.cn).Bonferroni corrected P-value was adopted for multiple comparisons.P<0.05 was considered as statistically significant.To further characterize the potential involvement of the GRIA1,GRM3 and TCF4 in schizophrenia,we constructed the interaction network to show the potential interactions between these three genes and other related proteins by using the high-confidence protein interaction databases Gene MANIA(http://www.genemania.org/).Power calculations were estimated using the Quanto 1.2.4 software.Results:1 Analysis of the association between GRIA1,GRM3 single nucleotide polymorphisms and schizophreniaIn this research,we found that the allele frequency(P=0.0371)of GRIA1 SNP rs2926835 between the cases and controls was statistically significant.After Bonferroni correction,the difference was no longer significant(P=0.4083).For the SNP rs6465084 of GRM3,the P value remained statistically significant after Bonferroni correction(P=0.0273).The SNP rs6465084 may increase the risk of schizophrenia only in females(Bonferroni correction,P=0.0195).No significant association between the cases and controls were found in other SNPs of GRIA1 and GRM3.Moreover,the haplotype(A-G)and(G-G)composed of rs6465084(P=0.004)and rs12704290(P=0.018)showed significant difference between the cases and controls.2 Analysis of the association between TCF4 single nucleotide polymorphisms and schizophreniaIn this research,no significant association was found between TCF4 single nucleotide polymorphisms and schizophrenia.Conclusions:In this research,the SNP rs6465084 of GRM3 was found to be associated with the schizophrenia,the A allele may increase the risk of schizophrenia.And the SNP rs6465084 may increase the risk of schizophrenia only in females.No significant association between the cases and controls was found in other SNPs.