Pleiotropic Roles of Dyslexia Genes in Neurodevelopmental Language Impairments

描述（由申请人提供）：语言障碍的个人遭受广泛的终身，有害的社会经济后果，往往是由于学术成就低下和认知能力的自我感知降低。几种行为障碍包含语言障碍作为诊断基础，包括阅读障碍、言语声音障碍（SSD）、特定语言障碍（SLI）和自闭症谱系障碍（ASD）。观察到的共同发生和重叠的临床表现，这些疾病之间的阅读障碍，SSD，SLI和ASD共享的决定因素。过去的研究表明，在这些不同的疾病中有相同的基因和基因组区域。然而，在何种程度上阅读障碍，SSD，SLI和ASD共享遗传决定因素仍有待评估。因此，这些研究的总体目标是确定阅读障碍、SSD、SLI和SSD的共同和独特的遗传决定因素。该假说是已知的阅读障碍基因将有助于观察到的语言障碍的SSD，SLI和ASD。这些核心语言基因的识别可能会导致针对各种语言障碍及其核心缺陷的干预措施的开发和实施。为了验证这一假设，六个不同的队列将检查阅读障碍基因对SSD，SLI和ASD语言障碍的贡献。本研究计划将通过使用多种流行病学和遗传设计，独立确定阅读障碍、SSD、SLI和ASD的共同和独特遗传决定因素。具体来说，这项研究的目的是：1）评估阅读障碍基因对SSD和SLI的贡献2）确定阅读障碍基因对ASD语言缺陷的贡献3）比较和评估与阅读障碍有关的基因在群体中的影响确定这些基因对语言的具体和整体影响将证明哪些基因导致某些语言障碍，哪些基因控制核心语言技能。这些目标的完成将用于未来的研究，以开发临床工具来诊断全球和特定的语言缺陷。此外，未来的分析将有助于创建遗传信息干预措施，针对疾病共享的核心语言缺陷和受影响儿童特有的障碍。

DESCRIPTION (provided by applicant): Individuals with language impairment suffer from a wide-range of lifelong, detrimental socioeconomic consequences frequently resulting from academic under-achievement and reduced self-perception of cognitive abilities. Several behavioral disorders contain language impairment as a diagnostic basis, including dyslexia, Speech Sound Disorder (SSD), Specific Language Impairment (SLI), and Autism Spectrum Disorders (ASD). Observed co-occurrence and overlap of clinical presentation among these disorders suggest dyslexia, SSD, SLI, and ASD share determinants. Past studies have implicated the same genes and genomic areas in these various disorders. However, to what extent dyslexia, SSD, SLI, and ASD share genetic determinants remains to be evaluated. Thus, the overall goal of these investigations is to determine the shared and unique genetic determinants of dyslexia, SSD, SLI, and SSD. The hypothesis is known dyslexia genes will contribute to the observed language impairment in SSD, SLI, and ASD. Identification of these core language genes could lead to the development and implementation of interventions targeting a variety of language disorders and their core deficits. To test this hypothesis, six different cohorts will examine the contribution of dyslexia genes to language impairments in SSD, SLI, and ASD. This study plan will identify shared and unique genetic determinants of dyslexia, SSD, SLI, and ASD independently through the use of multiple epidemiological and genetic designs. Specifically, the study aims to: 1) Evaluate the contribution of dyslexia genes to SSD and SLI 2) Determine the contribution of dyslexia genes to language deficits in ASD 3) Compare and evaluate effects of genes implicated in dyslexia among cohorts Determining the specific and global effects of these genes on language will demonstrate which genes cause certain language impairments and which control core language skills. Completion of these aims will be utilized in future investigations to develop clinical tools to diagnose global and specific language deficits. Additionally, future analyses will aid in creating genetically informed interventions that target both core language deficits that disorders share and impairments specific to the affected children.