Identification of genomic regions associated with schizophrenia using exploratory eye movements

一种与精神分裂症遗传易感性相关的生物学标记可能导致鉴定精神分裂症疾病的主要易感性位点。我们之前对负责探索性眼动（EEM）的基因座的全基因组扫描研究揭示了EEM和22q之间的显著联系，EEM可能与精神分裂症相关。鉴定22q染色体上与EEM表型相关的基因可能有助于我们对精神分裂症病因学的理解。为了确定22q上与精神分裂症相关的基因组区域，我们研究了22q与精神分裂症的关系。共分析了68个家庭274名成员。每个家庭至少包括一名精神分裂症患者，对1505名不相关的日本受试者进行了删除筛查。检测短序列重复多态性（STRPs）和单核苷酸多态性（snp）并进行基因分型，以评估连锁不平衡（LD）区。LD块通过GOLD程序计算，LD/与精神分裂症的关联通过传递不平衡测试（TDT）评估。除22q11.2、22q12.1、22q12.3外，在22q12.3中还筛选出APOL1、APOL2、APOL3、APOL4 4个基因突变。该研究得到了日本大学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STRPs，并检测到与精神分裂症相关的LD块。我们还发现APOL1和APOL4基因的基因组邻近区域与精神分裂症有关。我们清楚地证明，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