Pleiotropic Roles of Dyslexia Genes in Neurodevelopmental Language Impairments

描述(由申请人提供)：语言障碍患者遭受广泛的终生有害的社会经济后果，通常是由于学业成绩不佳和认知能力的自我认知能力下降造成的。一些行为障碍将语言障碍作为诊断基础，包括诵读困难、语音障碍(SSD)、特定语言障碍(SLI)和自闭症谱系障碍(ASD)。观察到这些疾病的共同出现和临床表现的重叠表明阅读困难、SSD、SLI和ASD具有共同的决定因素。过去的研究表明，相同的基因和基因组区域与这些不同的疾病有关。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。已知阅读障碍基因会导致SSD、SLI和ASD中观察到的语言障碍。识别这些核心语言基因可以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验阅读障碍基因对SSD、SLI和ASD语言障碍的贡献。这项研究计划将通过使用多种流行病学和基因设计，独立地确定阅读障碍、SSD、SLI和ASD的共同和独特的遗传决定因素。具体地说，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)在队列中比较和评估与阅读障碍有关的基因的影响，确定这些基因对语言的具体和整体影响，以揭示哪些基因导致了特定的语言障碍，哪些基因控制了核心语言技能。这些目标的完成将被用于未来的研究，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疾病共有的核心语言缺陷和受影响儿童特有的障碍的遗传知情干预措施。 公共卫生相关性：语言障碍儿童因学业成绩不佳和认知技能自我认知能力下降而遭受一系列终身社会和经济后果。这些调查旨在确定多种疾病的共同基因，以便能够进行早期诊断，并在生命早期使用最有效的生物知情干预措施。未来的分析将有助于创建基因知情干预措施，既针对障碍共有的核心语言缺陷，也针对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. 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.