An Association Study of Neurogenin 1 and Schizophrenia

Neurogenin 1 与精神分裂症的关联研究

• 批准号: 6459760
• 负责人: AYMAN H FANOUS
• 金额: $ 7.5万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-06 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6459760
• 关键词: biotechnology; clinical research; family genetics; gene expression; gene mutation; genetic markers; genetic polymorphism; genetic susceptibility; genotype; human subject; interview; linkage disequilibriums; linkage mapping; mental disorder diagnosis; mental health epidemiology; nucleic acid sequence; polymerase chain reaction; schizophrenia; statistics /biometry

DESCRIPTION: (provided by applicant) Schizophrenia is a leading public health problem worldwide. Discovering genes that confer susceptibility to it is an important priority, as this may lead to the development of effective modalities of prevention and treatment. Although data from family, twin, and adoption studies suggest a genetic basis to schizophrenia, and several chromosomal regions have been linked to it, cloning susceptibility genes has been elusive. A specific and overarching pathophysiology of the disease has also been elusive, but evidence from neuroimaging and neuropathological studies converges to suggest that abnormal neurodevelopment may be a cause. In recent years, the biological events underlying neurodevelopment have begun to be uncovered, and several molecules that are involved in this process have been identified. One of these is neurogenini, which is involved in neuronal determination, specification of the molecular phenotype of neurons, and regional patterning of the cerebral cortex and thalamus. The gene for neurogenini is located on chromosome 5q, which has been implicated in several linkage studies of schizophrenia, including the Irish Study of High Density Schizophrenia Families (ISHDSF), which we propose to study. It is located very close to some of the most highly linked markers in this region. We propose to perform an association study of neurogenin1 and schizophrenia. As there are no known sequence variants, we propose to sequence this gene in 25 schizophrenics from the ISHDSF. We then intend to test any variants that are discovered for association with the disease. To do this, we plan to genotype all triads consisting of two parents and one affected offspring in the ISHDSF, supplemented by an additional triad collection currently underway in Ireland. We will use the transmission disequilibrium test, which determines Wan allele is transmitted to an affected offspring more often that expected by chance, to test for association and linkage. We also propose to test whether any of the variants modifies any of the clinical features of the disease. To do this, we plan to regress symptom scores on three factors as well as individual symptoms onto the transmission status of the allele, using logistic regression. If there are resources left over, we plan to genotype 400 normal controls and perform a case-control analysis using a chi-squared test to confirm any suggestive findings.

描述：（由申请人提供）精神分裂症是一种主要的公共卫生 全世界的问题。发现基因赋予它的易感性是一个 重要的优先事项，因为这可能导致制定有效的模式 预防和治疗。虽然来自家庭双胞胎和收养的数据 研究表明，精神分裂症的遗传基础， 区域已经与它联系在一起，克隆易感基因一直是难以捉摸的。 该疾病的具体和总体病理生理学也已被证实。 难以捉摸，但来自神经影像学和神经病理学研究的证据 表明异常的神经发育可能是一个原因。近年来 神经发育背后的生物学事件已经开始被发现， 已经鉴定了参与该过程的几种分子。一 其中包括neurogenini，它参与神经元的决定， 神经元的分子表型的规范，以及神经元的区域模式化。 大脑皮层和丘脑。neurogenini的基因位于 染色体5q，这已经牵连在几个连锁研究， 精神分裂症，包括爱尔兰高密度精神分裂症家庭研究 （ISHDSF），我们建议进行研究。它位于非常接近的一些 最紧密相连的标记 我们建议进行一项关联研究神经生成素1和精神分裂症。作为 没有已知的序列变异，我们建议在25个基因中对该基因进行测序。 ISHDSF的精神分裂症患者然后，我们打算测试任何变体， 发现与疾病有关。为了做到这一点，我们计划基因分型 ISHDSF中的所有三联体均由双亲和一个受影响的后代组成， 目前正在爱尔兰进行的另一项三合会收集工作也是一个补充。 我们将使用传播不平衡检验，确定Wan等位基因 传染给受影响的后代比预期的更频繁， 测试关联和链接。我们还建议测试 变异改变了疾病的任何临床特征。为此我们 计划回归三个因素以及个体症状的症状评分 等位基因的传播状态，使用逻辑回归。如果 剩余的资源，我们计划对400名正常对照进行基因分型， 使用卡方检验进行病例对照分析，以确认任何提示 调查结果。