Genetic linkage and association between chromosome 1q and working memory function in schizophrenia
Genetic linkage and association between chromosome 1q and working memory function in schizophrenia
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DOI：
10.1002/ajmg.b.10757
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发表时间：
2003-01-01
影响因子：
2.8
通讯作者：
Cannon, TD
中科院分区：
文献类型：
--
作者：
Gasperoni, TL;Ekelund, J;Cannon, TD
精神分裂症基本上是遗传的，但具体的易感基因仍有待确定。这奋进的进展受到了非孟德尔传播模式、可能的遗传异质性以及无法检测到易感基因的发病前和非渗透性携带者的阻碍。为了规避这些复杂性，本研究采用了定量措施的责任，或“内表型”，在一个样本的双胞胎不一致的精神分裂症，从相对遗传隔离的人口芬兰。在之前的两项使用芬兰患者样本的研究中，1号染色体远端部分的一个区域显示出与精神分裂症相关的证据。为了进一步阐明这种潜在的易感基因的性质和位置，使用定量神经心理学方法对1号染色体感兴趣区域进行了连锁和关联分析。分析与复合措施的责任产生了暗示性的证据，在标记D1 S2833（P = 0.04）的联系。个体特征测量的后续分析表明，韦氏记忆量表（WMS），空间工作记忆功能的指标，视觉跨度子测试是唯一敏感的标记D1 S2833（P=0.007）。关联分析证实，D1 S2833中的等位基因变异与通过视觉广度子测试测量的空间工作记忆表现的变异相关（P = 0.003），其显著性在10，000个Monte Carlo排列的分析中得到证实。这些数据支持这种方法的实用性，并为影响精神分裂症患者及其未受影响的双胞胎的空间工作记忆功能的基因提供了证据。(C)2003 Wiley-Liss，Inc.
Schizophrenia is substantially heritable, but specific susceptibility genes remain to be identified. Progress in this endeavor has been hindered by non-Mendelian transmission patterns, probable genetic heterogeneity, and an inability to detect premorbid and nonpenetrant carriers of predisposing genes. To circumvent these complexities, this study employed quantitative measures of liability, or "endophenotypes," within a sample of twins discordant for schizophrenia, drawn from the relatively genetically isolated population of Finland. A region on the distal portion of chromosome 1 has shown evidence for linkage to schizophrenia in two prior studies using Finnish patient samples. To elucidate further the nature and location of this potential susceptibility gene, linkage and association analyses were carried out across the chromosome 1 region of interest using quantitative neuropsychological measures of liability. Analyses with a composite measure of liability yielded suggestive evidence for linkage at marker D1S2833 (P = 0.04). Follow-up analyses of the individual trait measures showed that the Visual Span subtest of the Wechsler Memory Scale (WMS), an indicator of spatial working memory function, was uniquely sensitive to marker D1S2833 (P=0.007). Association analysis confirmed that allelic variation in D1S2833 is associated with variation in spatial working memory performance as measured by the Visual Span subtest (P = 0.003), the significance of which was confirmed in an analysis of 10,000 Monte Carlo permutations. These data support the utility of this approach and provide evidence for a gene affecting spatial working memory function in schizophrenia patients and their unaffected co-twins. (C) 2003 Wiley-Liss, Inc.