Replication of linkage on chromosome 7q22 and association of the regional Reelin gene with working memory in schizophrenia families
Replication of linkage on chromosome 7q22 and association of the regional Reelin gene with working memory in schizophrenia families
复制标题
DOI：
10.1038/sj.mp.4002047
复制
发表时间：
2008-07-01
影响因子：
11
通讯作者：
Peltonen, L.
中科院分区：
文献类型：
--
作者：
Wedenoja, J.;Loukola, A.;Peltonen, L.
精神分裂症是一种常见而复杂的精神障碍。遗传因素对该病的病因很重要，但尽管在不同人群的几个染色体区域报告了连锁信号，但最终确定易感基因仍然是一个挑战。利用来自芬兰的一个大型家庭精神分裂症研究样本，我们已经确定了几个连锁基因座：1q32.2-q42，2q，4q31，5q和7q22。在这项研究中，352个核心精神分裂症家系(n=1626)的独立样本允许在7q21-32上复制连锁。在245个核心家系(n=1074)中，对GRM3、RELN、SEMA3A和VGF这四个区域候选基因进行SNP和微卫星关联分析，发现它们与精神分裂症的临床诊断没有显著关联。取而代之的是，从186个核心家庭(n=861)获得的神经心理内表型的可量化特征成分分析显示，与语言(P=0.000003)和视觉工作记忆(P=0.002)、记忆(P=0.002)和执行功能(P=0.002)相关的特征与RELN变量显著相关。特征相关等位基因阳性的受试者在工作记忆(P=0.0004-0.0000000004)、记忆(P=0.02-0.0001)和执行功能(P=0.001)的测试中得分较低。我们的发现表明，RELN的等位基因变异与精神分裂症的内表型有关。
Schizophrenia is a common and complex mental disorder. Hereditary factors are important for its etiology, but despite linkage signals reported to several chromosomal regions in different populations, final identification of predisposing genes has remained a challenge. Utilizing a large family-based schizophrenia study sample from Finland, we have identified several linked loci: 1q32.2-q42, 2q, 4q31, 5q and 7q22. In this study, an independent sample of 352 nuclear schizophrenia families (n = 1626) allowed replication of linkage on 7q21-32. In a sample of 245 nuclear families (n = 1074) originating from the same geographical region as the families revealing the linkage, SNP and microsatellite association analyses of the four regional candidate genes, GRM3, RELN, SEMA3A and VGF, revealed no significant association to the clinical diagnosis of schizophrenia. Instead, quantifiable trait component analyses with neuropsychological endophenotypes available from 186 nuclear families (n = 861) of the sample showed significant association to RELN variants for traits related to verbal (P = 0.000003) and visual working memory (P = 0.002), memory (P = 0.002) and executive functioning (P = 0.002). Trait-associated allele-positive subjects scored lower in the tests measuring working memory (P = 0.0004-0.0000000004), memory (P = 0.02-0.0001) and executive functioning (P = 0.001). Our findings suggest that allelic variants of RELN contribute to the endophenotypes of schizophrenia.