Pleiotropic Roles of Dyslexia Genes in Neurodevelopmental Language Impairments

描述（由申请人提供）：有语言障碍的个体遭受着广泛的、终身的、有害的社会经济后果，这些后果通常是由于学业成绩不佳和认知能力自我认知能力下降造成的。一些行为障碍包括语言障碍作为诊断基础，包括阅读障碍、语音障碍（SSD）、特殊语言障碍（SLI）和自闭症谱系障碍（ASD）。观察到这些疾病的共同发生和重叠的临床表现表明，阅读障碍、SSD、SLI和ASD有共同的决定因素。过去的研究表明，在这些不同的疾病中存在相同的基因和基因组区域。然而，阅读障碍、SSD、SLI和ASD在多大程度上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。这一假设是已知的，阅读障碍基因会导致SSD、SLI和ASD中观察到的语言障碍。这些核心语言基因的鉴定可能导致针对各种语言障碍及其核心缺陷的干预措施的发展和实施。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中语言障碍的贡献。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。具体而言，本研究旨在：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相关的基因在队列中的作用确定这些基因对语言的具体和整体影响将表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，以开发诊断全球和特定语言缺陷的临床工具。此外，未来的分析将有助于创建针对核心语言缺陷的遗传知情干预措施，这些缺陷既包括疾病共有的核心语言缺陷，也包括受影响儿童特有的缺陷。

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. PUBLIC HEALTH RELEVANCE: Children with language impairment suffer from a wide-range of lifelong social and economic consequences resulting from academic under-achievement and reduced self-perception of cognitive skills. These investigations aim to identify genes common to multiple disorders in order to permit earlier diagnoses and the use of biologically informed interventions early in life when it is most effective. 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.