An Association Study Between GRM5 Gene And Schizophrenia

Schizophrenia is a severe psychiatric disorder that affects about 1% of the world,s population.Data from twin, adoption, and family study show that genetic factors play important role in the etiology and the heritability is about 80%. At present, it is thought that schizophrenia is a multifactorial disease with multiple susceptibility genes of middle or small effects interacting with each other and environmental factors also influence susceptibility of the disease. A positive finding from our previous whole genome association study by using of Affymetrix Genome-Wide Human SNP Array 6.0. a SNP locus within GRM5 gene was found to be associated with schizophenia. We then selected and genotyped the 6 SNPs individually to investigate association between GRM5 gene and schizophrenia by high resolution melting (HRM) genotyping system.ObjectiveTo validate the association between GRM5 and schizophrenia which was previously detected positive by our genome screen and some research abroad.MethodsFirstly,89 childhood and adolescent onset schizophrenia and 1000 normal controls were screened by affymetrix 6.0 microarray in pooled DNA , and rs16915130 was detected positive( X2 = 39.895 P=2.68×10-10).Secondly, 100 childhood and adolescent onset schizophrenia nuclear families were genotyped by six single nucleotide polymorphism (SNP) ( rs591849,rs16915130,rs3899716,rs2133395,rs597462 and rs1942486)by High-Resolution Melting (HRM) system. Alellic and haplotipic association of the 6 SNPs were analyzed by Haploview 4.1 software.ResultsThe data analysis of the two DNA pooling samples genotyped by Affymetrix Genome-Wide Human SNP Array 6.0 revealed that rs16915130 was associated with Schizophrenia ( X2 = 39.895 P=2.68×10-10). This SNP is just within the GRM5 gene. The data analysis of the six SNPs (rs591849,rs16915130,rs3899716,rs2133395,rs597462 and rs1942486) genotyped in the 100 families were all in Hardy–Weinberg equilibrium. However, no association was detected either in the single marker analysis and haplotypes.Conclusions:GRM5 gene is unlikely to play an important role in the etiology of childhood and adolescent onset schizophrenia in Shandong province of China.