Linkage analysis of schizophrenia using exploratory eye movement dysfunction

目的：到目前为止，一些研究已经证明了不同染色体位点的DNA标记与精神分裂症的联系。然而，这些联系的发现在研究中并不完全一致。在本研究中，为了克服精神分裂症连锁分析的困难，我们采用了全基因组连锁分析，而没有使用精神分裂症的诊断分类作为表型。我们使用了定量性状测量（探索性眼动：EEM），这与精神分裂症作为表型密切相关。方法：对38个核心家庭共122个成员（38个先证，47个兄弟姐妹和37个父母）的58对兄弟姐妹进行EEM干扰与358个高多态性微卫星标记的10 cm（厘米）全基因组连锁分析。结果：22q11染色体上的GCT10C10标记在参数QTL分析中获得显著连锁（LOD=3.48, p=3.1x10^<-5>）。在非参数分析中，GCT10G10标记的p值也最小（Z=2.27, p=0.012）。结论：我们的研究结果表明，使用特定的精神分裂症数量性状可能为精神分裂症的连锁分析提供增强的力量。我们认为EEM特征可能是鉴定精神分裂症病因相关基因的一个有前途的工具。我们还认为，NEFRS的连锁数据，特别是22q11染色体的连锁数据，可能是检测精神分裂症相关基因的有希望的线索。

Objective : To date, several studies have demonstrated linkage of DNA markers in various chromosomal sites to schizophrenia. However, these linkage findings have not been completely consistent across studies. In this study, to surmount the difficulties in linkage analysis of schizophrenia, we employed genome-wide linkage analysis without utilizing diagnostic classification of schizophrenia as the phenotype. We used quantitative trait measure (exploratory eye movement : EEM), which was closely correlated with schizophrenia as the phenotype. Method : A 10-cM(centimorgan) resolution genome-wide linkage analysis between EEM disturbance and 358 highly polymorphic microsatellite markers in 38 nuclear families with 122 members(38 probands, 47 siblings and 37 parents) including 58 sib-pairs was performed. Results : The GCT10C10 marker on chromosome 22q11 yielded the significant linkage (LOD=3.48, p=3.1x10^<-5>)in parametric QTL analysis. The smallest p value was also observed at the GCT10G10 marker (Z=2.27, p=0.012) in nonparametric analysis. Conclusion : Our findings suggest that the use of specific quantitative trait of schizophrenia may offer augmented power in linkage analysis of schizophrenia. We propose that the EEM trait may be a promising tool for identifying gene(s) relating to etiology of schizophrenia.We also consider that linkage data of the NEFRS, paticularlyfor chromosome 22q11, may be promising hints for detecting gene(s) associated with schizophrenia,