Investigation on candidate genes based upon the pathophysiological hypotothesis of schizophrenia

基于精神分裂症的低血糖假说，我们对VGLUT 1/2和ASCT 1/2基因进行了病例对照关联研究。在VGLUT 1基因区域检测到LD阻断，单倍型分析显示名义上显著的关联（P=0.06）。IVS 2 + 87 A>G与偏执型精神分裂症有显著相关性（P = 0.01）。在VGLUT 2基因区检测到两个LD阻断，但病例组和对照组之间的等位基因型频率无显著差异。IVS 2 - 49 G>A与女性精神分裂症的发生有显著相关性（P = 0.02）。我们对50名精神分裂症患者的DISC 1基因进行了重新测序。我们检测到32个新的突变，包括10个错义变异。这些结果支持常见病多罕见变异假说。

We performed case-control association study for VGLUT1/2 and ASCT1/2 gene based upon the hypoglutamatergic hypothesis of schizophrenia. A LD block was detected in VGLUT1 gene region and haplotype analysis showed nominally significant association (P=0.06). IVS2+87A>G displayed significant association with paranoid type schizophrenia (P = 0.01). Two LD blocks were detected in VGLUT2 gene region but haplytype frequencies showed no significant different between cases and controls. IVS2-49G>A was significantly associated with female schizophrenia (P = 0.02). Those associations were not significant after Bonffeioni's correction.We resequenced DISC1 gene using 50 schizophrenia having affected relatives. We detected 32 novel mutations including 10 missense variants. These results supported common disease multiple rare variants hypothesis.