儿童青少年精神分裂症与GRM5基因的全基因组关联分析和家系对照研究

The genome-wide association and family based association studies of the GRM5 gene with childhood and adolescent onset schizophrenia

目的对既往有阳性发现的促代谢型谷氨酸受体5基因(glutamate receptor,metabotropic 5,GRM5)与精神分裂症的关联进行验证。方法先用affymetrix 6.0芯片对89例儿童青少年精神分裂症与1000例正常对照的DNA分别进行全基因组关联分析,而后在另一个样本-100个儿童青少年精神分裂症核心家系中采用高分辨率溶解曲线(High Resolution Melting,HRM)进行了GRM5基因6个SNP位点(rs591849,rs16915130,rs3899716,rs2133395,rs597462,rs1942486)的检测。用HaploView4.1软件进行数据的统计分析。结果 89例儿童青少年精神分裂症与1000例正常对照的全基因关联分析显示,GRM5基因的rs16915130位点与精神分裂症存在关联(x2=39.895,P=2.68×10-10),然而通过6个SNP位点及所构建的单倍型在儿童青少年精神分裂症家系的验证却不支持GRM5基因与精神分裂症关联(P>0.05)。结论本研究不支持GRM5基因与儿童青少年精神分裂症关联。

Objective To verify the association between GRM5 gene and schizophrenia Methods The genome wide association study （GWS） was performed on 89 childhood and adolescent onset schizophrenia and 1000 normal controls using affymetrix 6.0 microarray. Six single nucleotide polymorphism （SNP） （ rs591849, rs16915130, rs3899716, rs2133395, rs597462 and rs1942486）were detected in 100 childhood and adolescent onset schizophrenia nuclear families u sing High-Resolution1 Melting （HRM） system. Haploview 4. 1 software was used to analyzed alellic and haplotipic association of the SNPs. Results GWS revealed an association of rs16915130 with schizophrenia. However, no association were detected in either allelie or haplotypic analysis in those families （P 〉 0.05 ）. Conclusions Our data have not confirmed the association of GRM5 gene with the etiology of childhood and adolescent onset schizophrenia in Shandong province of Chi na