Twins and Singletons with Specific Language Impairment

具有特定语言障碍的双胞胎和单胞胎

基本信息

批准号：
9088444
负责人：
MABEL L RICE
金额：
$ 46.68万
依托单位：
UNIVERSITY OF KANSAS LAWRENCE
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-07-05 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9088444
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 Genetic study 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 Research Design Risk Sampling Schools Site Speech Time Translating Translations Twin Multiple Birth age effect base clinical application cognitive development cognitive skill cohort expectation language impairment language onset longitudinal course methylation pattern population based proband prognostic programs skills social specific language impairment temporal measurement

项目摘要

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）：该调查程序的架构目标是确定特定语言障碍（SLI）的发病机理和个体发育。这一资金周期的具体目的是：1）记录2-14岁双胞胎的纵向语言获取，并与2、6、9和14岁的单身人士进行比较； 2）确定对早期语言获取的双重影响，并描述这种影响的纵向过程； 3）开发针对双胞胎效应和SLI的生物学和环境风险的多元模型，并比较可能的重叠病因； 4）通过融合方法评估年龄段的遗传效应模型。评估了以下三个假设：首先，语言能力的发展变化是通过基因表达随着时间的变化而介导的，这些变化部分是甲基化模式的变化介导的，鉴于最新的甲基化替代较高认知障碍的证据。其次，基因表达的异常是通过调节部位中异常甲基化模式的某些类型语言损害的基础。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，这些效应可以阐明某些影响语言发作风险的影响，这些风险可能会随着时间的流逝而调节，从而使强大的持续持续性SLI风险持续。这项研究扩展了1460名双胞胎儿童，他们的家庭成员和237名对照儿童的当前滞后纵向研究，在14年时进行了第五次测量，以增加2、4、6和9年的纵向评估。该协议包括广泛的家庭和环境数据，以及包括阅读在内的语言，语音和认知技能的详细协议。此外，在14年的时间里，测量值将在儿童为成人生活的准备时捕捉到他们的社会和学术变异性。在这一资金周期中，数据收集将完成家庭DNA和行为评估，按照双胞胎和单顿探针的完整样本相同的协议。研究设计结合了与大型单例基于大量的社会，认知和学术评估相比，通过与大型单人群的样本进行比较来评估双胞胎效应的独特机会。在分子遗传学水平上，将进行基于家庭的靶基因研究，以及对不一致的MZ Co-Twins中甲基化调控的首次研究。这些发现将记录语言增长，并确定这种增长的遗传，表观遗传和环境驱动力。结果的潜在临床翻译包括更好的诊断方法，以识别双胞胎和单例中的SLI，以确定长期风险的SLI，阅读障碍和青少年适应性有限的儿童；并确定增长定义的干预目标，以实现语言获取的特定维度。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Jurisdictional, socioeconomic and gender inequalities in child health and development: analysis of a national census of 5-year-olds in Australia.

DOI：
10.1136/bmjopen-2012-001075
发表时间：
2012
期刊：
BMJ open
影响因子：
2.9
作者：
Brinkman SA;Gialamas A;Rahman A;Mittinty MN;Gregory TA;Silburn S;Goldfeld S;Zubrick SR;Carr V;Janus M;Hertzman C;Lynch JW
通讯作者：
Lynch JW

Fetal head circumference growth in children with specific language impairment.

有特定语言障碍的儿童的胎儿头围生长。