Project: Epigenetics, Polygenic Risk and the Social Environment in Autism

项目：自闭症的表观遗传学、多基因风险和社会环境

基本信息

批准号：
10669151
负责人：
Lane Strathearn
金额：
$ 27.27万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-16 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10669151
关键词：
3 year old Affect Age Anxiety Autism Diagnosis Behavior Birth Blood Brain Cellular Phone Child Clinical assessments Collection DNA DNA Methylation Data Day Care Development Developmental Delay Disorders Developmental Disabilities Devices Diagnosis Disease Dryness Early Intervention Ecological momentary assessment Emotional Enrollment Environment Environmental Risk Factor Epigenetic Process Ethnic Origin Etiology Exclusion Family Genetic Genetic Predisposition to Disease Genetic study Genomics Goals Home Individual Intellectual and Developmental Disabilities Research Centers Intellectual functioning disability Intervention Iowa Language Learning Life Longevity Longitudinal Studies Measures Mediating Mental Depression Methylation Modeling Modification Mothers Neuropeptides Newborn Infant Oranges Outcome Oxytocin Oxytocin Receptor Perinatal Play Pregnancy Prevalence Prevention strategy Race Receptor Gene Research Research Project Grants Resources Rest Risk Risk Assessment Risk Marker Role Sampling Scanning Site Social Development Social Environment Societies Socioeconomic Status Spottings Stress Testing Time United States Universities adolescent with autism spectrum disorder autism spectrum disorder autistic behaviour autistic children clinical translation cognitive development cohort cost estimate disability disability risk educational atmosphere experience innovation neural circuit polygenic risk score prospective prototype rare condition receptor recruit repetitive behavior sex smartphone application social social communication trait

项目摘要

ABSTRACT: RESEARCH PROJECT Intellectual and developmental disabilities (IDD) affect up to one in six children in the United States, with proposed etiologies ranging from genetic to multi-factorial. For a vast majority of children, no clear genetic or environmental etiology is identified, although evidence suggests that genetic (intrinsic) risk may interact with the early learning and social environment (extrinsic risk) to predict neurodevelopmental outcomes in later stages of life. For example, the neuropeptide oxytocin and its receptor (OXTR) are epigenetically altered by early social experience, play crucial roles in mammalian social and cognitive development, and are associated with both genetic and epigenetic risk for autism spectrum disorder (ASD). The objective of this Hawk-IDDRC Research Project is to examine epigenetic, polygenic and environmental risk factors for IDD, focusing on ASD as a prototype. We will use an innovative new smartphone application, BabySteps, to enroll and collect data on 300 mothers and their children between 2 and 3 years of age, over a 6-month period. One hundred and sixty ASD children will be enrolled, along with 80 children with non-ASD developmental delay (DD), and 80 typically developing (TD) control children, matched by race/ethnicity, sex and family socioeconomic status. We will examine changes in DNA methylation (DNAm) in 27 specific ASD-associated loci, as well as 3 OXTR loci, as a function of age and social experience, in children with and without autism, comparing DNAm from stored newborn dried blood spots to samples collected at the time of diagnosis. Polygenic risk scores for ASD will be calculated using Illumina PsychArray, and the relative polygenic and epigenetic risk assessed using resources from the Developmental Genomics/Epigenetics Core. The relationship between DNAm and social experience will be assessed using 2 complementary measures: 1) the Language Experience Analysis (LENA) based on audio recordings from a LENA device worn by the child over a 4-day period at home and in daycare; and 2) ecological momentary assessments (EMAs) of parental social and emotional availability collected using the BabySteps app. Children will be recruited through the Clinical Translational Core and Autism Center after ASD is either confirmed or excluded, based on ADOS testing and/or rigorous clinical assessment. A subset of 20 ASD and 20 TD children will participate in pilot resting state functional connectivity scanning through the Neurocircuitry and Behavior Core, to examine associations between DNAm of ASD-associated loci, including OXTR, and differences in brain connectivity. With the Administrative Core, we will share the BabySteps app with other Centers in the IDDRC Network and prospectively compare the effects of perinatal stress and social/learning experience on DNAm in children yet to be diagnosed with ASD. It is hypothesized that both polygenic factors and early social experience (via epigenetic modifications) contribute to ASD or IDD risk. Understanding how the environment interacts with genetic vulnerability will provide an unprecedented opportunity to re-assess early intervention and prevention strategies.

摘要：研究项目在美国，智力和发育障碍（IDD）影响多达六分之一的孩子提出的病因从遗传到多因素。对于绝大多数儿童，没有明确的遗传或鉴定了环境病因，尽管有证据表明遗传（内在）风险可能与早期的学习和社会环境（外部风险），以预测稍后的神经发育结果生活阶段。例如，神经肽催产素及其受体（OXTR）在表观上改变了早期的社交经验，在哺乳动物的社会和认知发展中扮演至关重要的角色，并与之相关具有自闭症谱系障碍（ASD）的遗传和表观遗传风险。这个鹰 - iddrc的目的研究项目将检查IDD的表观遗传，多基因和环境风险因素，重点关注ASD 作为原型。我们将使用创新的新智能手机应用程序BabySteps来注册和收集数据在6个月的时间内，有300名母亲及其孩子在2至3岁之间。一百六十 ASD儿童将与80个非ASD发育延迟（DD）一起入学，通常80名发展（TD）控制儿童，与种族/种族，性别和家庭社会经济地位相匹配。我们将检查27个特定ASD相关基因座以及3个OXTR基因座的DNA甲基化（DNAM）的变化，作为A 年龄和社交经验的功能，在患有和没有自闭症的儿童中，与存储的DNA进行比较诊断时新生的血液点归于收集的样品。 ASD的多基因风险分数将是使用Illumina Psycharay以及使用资源评估的相对多基因和表观遗传风险计算从发育基因组学/表观遗传学核心。 Dnam与社会之间的关系将使用2种互补措施评估经验：1）语言经验分析（LENA）基于孩子在家庭和日托中戴的Lena设备中戴的Lena设备的录音； 2）使用使用的父母社会和情感可用性的生态瞬时评估（EMA） Babysteps应用程序。儿童将通过临床翻译核心和自闭症中心招募根据ADOS测试和/或严格的临床评估，确认或排除ASD。一个子集 20个ASD和20个TD儿童将参加试点静止状态功能连接性通过神经记录和行为核心，检查与ASD相关基因座的DNAM之间的关联，包括OXTR，以及大脑连通性的差异。使用行政核心，我们将分享 BabySteps应用程序与IDDRC网络中的其他中心，并前瞻性地比较了围产期的影响尚未被诊断为ASD的儿童的DNA上的压力和社交/学习经验。它是假设的多基因因素和早期的社会经验（通过表观遗传修改）有助于ASD或IDD 风险。了解环境如何与遗传脆弱性相互作用将提供前所未有的重新评估早期干预和预防策略的机会。