Identification of genomic regions associated with schizophrenia using exploratory eye movements

一个与精神分裂症遗传易感性相关的生物标记可能会导致识别精神分裂症疾病的主要易感位点。我们以前的研究，全基因组扫描的一个位点负责探索性眼球运动（EEM），这可能是干扰与精神分裂症，揭示了EEM和22 q之间的显着联系。确定染色体22 q上与EEM表型相关的基因可能会促进我们对精神分裂症病因学的理解。为了寻找22 q上与精神分裂症相关的基因组区域，我们对68个家系274名成员的22 q进行了分析。每个家庭中至少包括一名精神分裂症患者。对1505名无关的日本受试者进行了缺失筛查。检测短重复序列多态性（STRP）和单核苷酸多态性（SNPs），并进行基因分型，以评估连锁不平衡（LD）块。LD块计算的GOLD程序和LD/与精神分裂症的关联进行了评估，通过传递不平衡检验（TDT）。除22q11.2、22q12.1和22q12.3外，还筛选了22q12.3中APOL 1、APOL 2、APOL 3和APOL 4四种基因的突变。本研究获得日本大学伦理委员会和筑波大学伦理委员会的批准，我们在22q11.2区域发现了新的STRP，并检测了与精神分裂症相关的LD阻断。我们还发现APOL 1和APOL 4基因的基因组邻近区域与精神分裂症相关。我们清楚地证明了PRODH基因的缺失不会大大增加精神分裂症的风险

A biological marker that is related to a genetic predisposition to schizophrenia could lead to identification of a major susceptibility locus for schizophrenic illness. Our previous study of a genome-wide scan for a locus responsible for exploratory eye movement (EEM), which can be disturbed in association with schizophrenia, revealed significant linkage between EEM and 22q. Identifying gene(s) on chromosome 22q associated with the EEM phenotype may forward our understanding of the etiology of schizophrenia. To identify genomic region(s) associated with schizophrenia on 22q, we examined 22q in association with schizophrenia.A total of 68 families with 274 members were analyzed. At least one schizophrenic patient was included in each family Deletion screening was performed for 1505 unrelated Japanese subjects. Short andem repeat polymorphisms (STRPs) and single nucleotide polymorphisms (SNPs) were detected and genotyped for assessing linkage disequilibrium (LD) blocks. LD blocks were computed by a GOLD program and LD/association with schizophrenia was assessed by transmission disequilibrium test (TDT). In addition to 22q11.2, 22q12.1, and 22q12.3, mutations were screened for four genes of APOL1, APOL2, APOL3, and APOL4 in 22q12.3. The study was approved by the Ethics Committees of Nihon University and University of Tsukuba.we identified novel STRPs in 22q11.2 region and detected LD blocks associated with schizophrenia. We also found that genomic neighboring regions of the APOL1 and APOL4 geneswere associated with schizophrenia. We clearly demonstrated that deletion of the PRODH gene do not raise a risk of schizophrenia greatly