A Family-Genetic Study of Language in Autism

描述(申请人提供)：自闭症是一种严重的神经发育障碍，经常给自闭症患者、他们的家庭和社会带来沉重的负担。旨在揭示这种疾病发病机制的研究可能导致以证据为基础的预防或治疗方法，因此具有重要意义。强有力的证据支持自闭症的遗传病因学，双胞胎和家庭研究也表明，自闭症患者的未受影响的亲属似乎通过与自闭症的定义特征更温和但质量上相似的特征来表达遗传倾向。这种亚临床语言和人格特征的星座通常被称为‘宽泛的自闭症表型’或‘BAP’。重要的是，尽管根据定义，自闭症涉及所有三个症状领域的严重损害，但有证据表明，这些特征可能与BAP的未受影响(患有自闭症)的亲属分离并独立存在。因此，对自闭症患者亲属的研究有助于简化复杂的自闭症表型，并识别比完整的临床综合征更容易进行基因解剖的组成部分特征。在这项研究中，我们专注于定义自闭症患者及其亲属中具有遗传意义的语言表型，这些表型可能应用于遗传学研究。使用家庭研究设计，我们提出了一套详细的心理语言评估组合，用于自闭症患者和对照组的家庭。这一系列客观的、从实验中得出的语言处理心理语言学测量结果可能会产生更清晰的发现，使目前对自闭症和BAP相关语言障碍的关键机制的理解更加清晰。结果还将提供可用于遗传学研究的量化措施，并可作为临床干预努力的目标。在拥有遗传学专业知识的高级合作研究人员的帮助下，我们将建立一个生物库，其中包括来自所有家庭的丰富表型和DNA样本，将用于未来的遗传学研究，更直接的是，跟进正在进行的几项大规模自闭症全基因组研究中肯定会出现的有希望的发现。 公共卫生相关性：本项目旨在确定自闭症遗传易感性的特定语言标记，这些标记可用于阐明自闭症的发病机制及其组成部分特征。旨在揭示自闭症发病机制的研究可能会导致基于证据的预防或治疗方法。

DESCRIPTION (provided by applicant): Autism is a severe, neurodevelopmental disorder that often confers a profound burden on autistic individuals, their families, and society. Research aimed at uncovering the pathogenesis of this condition may lead to evidence based approaches to prevention or treatment, and is therefore of great importance. Strong evidence supports a genetic etiology in autism, and twin and family studies have also shown that genetic liability appears to be expressed among unaffected relatives of people with autism through features that are milder, but qualitatively similar, to the defining characteristics of autism. This constellation of subclinical language and personality features is commonly referred to as the 'broad autism phenotype' or 'BAP'. Importantly, whereas by definition autism involves serious impairment across all three symptom domains, evidence suggests that such features may decouple and segregate independently in unaffected (with autism) relatives with the BAP. Therefore, studies of relatives of individuals with autism can help to simplify the complex autism phenotype and identify component traits which are more amenable to genetic dissection than the full clinical syndrome. In this study, we focus on defining genetically meaningful language phenotypes among individuals with autism and their relatives, that may be applied in genetic studies. Using a family study design, we propose a detailed psycholinguistic assessment battery for use in families of individuals with autism and controls. This battery of objective, experimentally derived psycholinguistic measures of language processing may produce findings that throw into sharper relief current understanding of key mechanisms underlying the language impairments associated with autism and the BAP. Results will also provide quantitative measures that may be used in genetic studies, and which could be targeted in clinical intervention efforts. With senior coinvestigators with expertise in genetics, we will establish a Biobank including these rich phenotypes and DNA samples from all families that will be used for future genetic studies, and more immediately, to follow up on promising findings sure to emerge from several largescale Genomewide studies of autism underway. PUBLIC HEALTH RELEVANCE: This project aims to identify specific linguistic markers of genetic liability to autism which may be used to illuminate the pathogenesis of autism and its component features. Research aimed at uncovering the pathogenesis of autism may lead to evidence-based approaches to prevention or treatment.