Twins and Singletons with Specific Language Impairment

具有特定语言障碍的双胞胎和单胞胎

• 批准号: 8683143
• 负责人: MABEL L RICE
• 金额: $ 48.69万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-05 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8683143
• 关键词: 14 year old; Adolescence; Adult; Affect; Age; Award; Behavior assessment; Behavioral Genetics; Biological Models; Child; Clinical; Cognition Disorders; Cognitive; Complex; DNA; Data; Data Collection; Development; Diagnostic Procedure; Dimensions; Documentation; Environmental Risk Factor; Epigenetic Process; Etiology; Family; Family member; Funding; Gene Expression; Gene Targeting; Genetic; Genetic Models; Genetic Risk; Growth; Heritability; Impairment; Inherited; Intervention; Investigation; Language; Language Development; Left; Life; Light; Longitudinal Studies; Measurement; Mediating; Methods; Methylation; Modeling; Molecular Genetics; Nursery Schools; Outcome; Participant; Pathogenesis; Pattern; Perinatal; Phenotype; Protocols documentation; Reading; Regulation; Relative (related person); Research Design; Risk; Sampling; Schools; Site; Speech; Time; Translating; Translations; Twin Multiple Birth; age effect; base; clinical application; cohort; expectation; language onset; longitudinal course; population based; proband; prognostic; programs; skills; social; specific language impairment

DESCRIPTION (provided by applicant): The over-arching objective of this program of investigation is to identify the pathogenesis and ontogeny of Specific Language Impairment (SLI). The specific aims for this cycle of funding are: 1)Document longitudinal language acquisition of twins ages 2-14 years, and compare to singletons at 2, 6, 9, and 14 years; 2) Identify twinning effects on early language acquisition and describe the longitudinal course of such effects; 3) Develop multivariate models of biological and environmental risk for twinning effects and for SLI, and compare for possible overlapping etiology; and 4) Evaluate models of age-graded genetic effects via converging methods. The following three hypotheses are evaluated: First, developmental changes in language ability are mediated through changes in gene expression over time, and these changes are mediated in part by changes in methylation patterns, in light of recent evidence of methylation alternations in higher cognitive disorders. Second, abnormalities in gene expression underlie some types of language impairment via abnormal methylation patterns in regulatory sites. Third, twinning effects reflect early complex interactions of genetic, perinatal, and environmental effects that can clarify some of the influences establishing risk for language onset, risks that may modulate over time leaving the robust ongoing risks for persistent SLI. The study extends a current lagged cohort longitudinal study of 1460 twin children, their family members, and 237 control children, with a fifth time of measurement at 14 years, to add to the obtained longitudinal assessments at 2, 4, 6, and 9 years. The protocol includes extensive family and environmental data as well as a detailed protocol of language, speech, and cognitive skills including reading. In addition, at 14 years the measurements will capture social and academic variability across children as they prepare for their transition to adult life. In this cycle of funding data collection will be completed for family DNA and behavioral assessments following the same protocol for the full sample of twin and singleton probands. The study design incorporates unique opportunities to evaluate twinning effects by comparison to large population-based samples of singletons on a wide variety of social, cognitive, and academic assessments. At the molecular genetics level, family-based target gene investigations will be conducted along with the first investigations of methylation regulation in discordant MZ co-twins. The findings will document language growth, and identify genetic, epigenetic, and environmental drivers of that growth. Potential clinical translations of the outcomes include better diagnostic methods, to identify SLI in twins as well as singletons, to identify children at long term risk for SLI, reading impairments, and limited adaptive outcomes in adolescence; and to identify growth-defined intervention targets for specific dimensions of language acquisition.

描述（由申请人提供）：该调查计划的首要目标是确定特定语言障碍（SLI）的发病机制和个体发育。本轮资助的具体目标是： 1）记录 2-14 岁双胞胎的纵向语言习得情况，并与 2、6、9 和 14 岁的单胞胎进行比较； 2）确定早期语言习得的孪生效应并描述这种效应的纵向过程； 3) 开发孪生效应和 SLI 的生物和环境风险多变量模型，并比较可能重叠的病因； 4) 通过收敛方法评估年龄分级遗传效应模型。评估以下三个假设：首先，语言能力的发育变化是通过基因表达随时间的变化而介导的，而这些变化部分是由甲基化模式的变化介导的，根据近期高级认知障碍中甲基化交替的证据。其次，基因表达异常是通过调控位点异常甲基化模式导致某些类型语言障碍的基础。第三，孪生效应反映了遗传、围产期和环境影响的早期复杂相互作用，可以澄清一些影响语言起始风险的因素，这些风险可能随着时间的推移而调节，从而为持续性 SLI 留下强大的持续风险。该研究扩展了当前一项对 1460 名双胞胎儿童、其家庭成员和 237 名对照儿童进行的滞后队列纵向研究，并在 14 岁时进行了第五次测量，以补充在 2、4、6 和 9 岁时获得的纵向评估。该协议包括广泛的家庭和环境数据以及语言、言语和认知技能（包括阅读）的详细协议。此外，在 14 岁时，测量将捕捉儿童在为向成年生活过渡做准备时的社会和学业差异。在此资助周期中，将按照双胞胎和单胎先证者完整样本的相同方案完成家庭 DNA 和行为评估的数据收集。该研究设计结合了独特的机会，通过在各种社会、认知和学术评估中与基于人口的大量单身样本进行比较来评估双胞胎效应。在分子遗传学水平上，基于家族的靶基因研究将与不一致的同卵双胞胎中甲基化调控的首次研究一起进行。研究结果将记录语言的增长，并确定语言增长的遗传、表观遗传和环境驱动因素。结果的潜在临床转化包括更好的诊断方法，识别双胞胎和单胎中的 SLI，识别处于 SLI 长期风险、阅读障碍和青春期适应性结果有限的儿童；并确定针对语言习得特定维度的增长定义的干预目标。