Autistic Traits: Life Course & Genetic Structure

自闭症特征：生命历程

• 批准号: 7690201
• 负责人: JOHN N. CONSTANTINO
• 金额: $ 57.35万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7690201
• 关键词: Accounting; Adolescence; Adolescent; Affect; African American; Age; Architecture; Arts; Asperger Syndrome; Attention deficit hyperactivity disorder; Autistic Disorder; Behavior; Behavioral; Biocompatible Materials; Biological Psychiatry; Brothers; Candidate Disease Gene; Caucasians; Caucasoid Race; Characteristics; Child; Childhood; Chromosome Arm; Clinical; Clinical Research; Collection; Complex; DNA; DSM-IV; Data; Data Linkages; Data Reporting; Data Set; Databases; Development; Developmental Process; Diagnosis; Diagnostic; Disadvantaged; Disease; Dysmorphology; Enrollment; Ethnic Origin; Ethnic group; Event-Related Potentials; Factor Analysis; Family; Family Study; Female; Funding; Gender; Gene Frequency; General Population; Generations; Genes; Genetic; Genetic Load; Genetic Structures; Genotype; Hispanics; Impaired cognition; Impairment; Incidence; Individual; Infant; Intervention; Interview; Life; Life Cycle Stages; Literature; Longevity; Longitudinal Studies; Manuals; Manuscripts; Measurement; Measures; Methods; Minority; Missouri; Modeling; Motor; Neurobiology; North Carolina; Nursery Schools; Outcome; Parents; Partner in relationship; Pattern; Phenotype; Population; Predisposition; Psychiatry; Public Health; Publishing; Questionnaires; Recruitment Activity; Registries; Reporting; Research; Research Personnel; Rest; Role; Sampling; Schedule; Schizoid Personality Disorder; Secure; Sensory; Severities; Siblings; Signal Transduction; Sister; Site; Social Development; Spouses; Stimulus; Structure; Study Subject; Susceptibility Gene; Symptoms; Testing; Time; Underrepresented Minority; Universities; Validation; Variant; Washington; autism spectrum disorder; base; design; endophenotype; family genetics; follow-up; functional disability; genetic linkage analysis; genetic pedigree; genetic resource; grandparent; indexing; infancy; intergenerational; intervention effect; longitudinal course; member; novel; phenome; primary outcome; proband; programs; public health relevance; relating to nervous system; response; segregation; social; social communication; somatosensory; teacher; trait; transmission process; treatment effect; volunteer

DESCRIPTION (provided by applicant): This is an application for a 5-year competing continuation of an ongoing longitudinal (R01) study of autistic social impairment in sibling pairs. Given recent findings regarding the genetic and neurobiologic architecture of autism, it has become clear that a more precise characterization of heritable quantitative components of the autism phenome might accelerate the discovery of specific genetic and neurobiologic causes of autism. This study will involve quantitative phenotyping of 5576 subjects (from 1295 clinically ascertained families of children with and without autism spectrum disorders (ASD). It will include: assessment of parents and affected individuals in extended pedigrees; examination of whether patterns of distribution of quantitative autistic traits in families vary as a function of gender, ethnicity, simplex versus multiplex versus "complex" autism, or other phenotypic covariates; longer-term follow-up of existing longitudinal study subjects to better elucidate the developmental course of autistic social impairment over time; and examination among sib-pairs of novel quantitative endophenotypes (motor, somatosensory, and electrophysiologic) that may relate both to severity of autistic social impairment and to core genetic and neurobiologic determinants of autism. In this application, we have attempted to be responsive to the problem that previous family-genetic studies of autism have often under-represented minority and disadvantaged populations, for whom specific liabilities to autism (if present) would be overlooked in existing studies and data sets. In addition to enhanced phenotypic characterization of this large clinically-ascertained sibling sample, 475 of the families will be genotyped (parents and sibling sets) by either of two ongoing national linkage studies of autism (the Autism Genetic Resource Exchange and the Simons Simplex Collection). In addition to implications for the genetics and neurobiology of autism, the findings from the study will enhance methods for measuring subtle effects of treatment, will identify intervals in the lifespan when interventions might have particular influence on social development, and will elucidate the manner in which functional disability incurred by a wide range of non-ASD child psychiatric conditions, including ADHD can be exacerbated when superimposed (as is common) by the co-occurrence of sub clinical autistic traits. PUBLIC HEALTH RELEVANCE: Autism and related disorders affect 1 out of every 150 children in the US and result in profound social impairment throughout life. This study examines how autistic social impairments change over the course of childhood, how they are transmitted across generations, and which normal developmental processes they disrupt. The results of the study will aid in the search for the genes and neural abnormalities that cause autism, will enhance methods for measuring subtle but important effects of intervention, and will identify intervals in the lifespan when interventions might have their greatest impact on social development in affected children.

描述(由申请人提供)：这是一项正在进行的关于兄弟姐妹中的自闭症社会损害的纵向(R01)研究的5年竞争性延续的申请。鉴于最近关于自闭症的遗传和神经生物学结构的发现，对自闭症现象组可遗传数量成分的更精确的表征可能会加速发现自闭症的特定遗传和神经生物学原因。这项研究将涉及5576名受试者(来自1295个临床确定的患有和不患有自闭症谱系障碍(ASD)的儿童家庭)的定量表型。它将包括：评估扩展家系中的父母和受影响的个人；检查自闭症数量特征在家庭中的分布模式是否随着性别、种族、单一自闭症与复杂自闭症或其他表型协变量的变化而变化；对现有纵向研究对象进行较长期的随访，以更好地阐明自闭症社会损害的发展过程；以及 SIB-一对新的定量内表型(运动、躯体感觉和电生理)，可能与自闭症社会损害的严重程度以及自闭症的核心遗传和神经生物学决定因素有关。在这项申请中，我们试图回应这样一个问题，即以前关于自闭症的家庭遗传学研究往往没有充分代表少数群体和弱势群体，对他们来说，自闭症的具体风险(如果存在)将在现有的研究和数据集中被忽视。除了这一大型临床确定的兄弟姐妹样本的增强表型特征外，475个家庭将通过正在进行的两项关于自闭症的全国性连锁研究(自闭症遗传资源交换和Simons Simplex Collection)中的任何一项进行基因分型(父母和兄弟姐妹集)。除了对自闭症的遗传学和神经生物学的影响外，这项研究的发现还将加强衡量治疗微妙效果的方法，将确定干预措施可能对社会发展产生特殊影响的生命间隔，并将阐明广泛的非自闭症儿童精神疾病，包括ADHD，在叠加(正如常见的)时，会以何种方式加剧功能障碍。 亚临床自闭症特征的共现。与公共健康相关：在美国，每150名儿童中就有一名患有自闭症和相关疾病，并导致终生严重的社会损害。这项研究考察了自闭症患者的社会障碍在以下过程中的变化 儿童时期，它们如何在世代之间传播，以及它们扰乱了哪些正常的发育过程。这项研究的结果将有助于寻找导致自闭症的基因和神经异常，将改进衡量干预措施微妙但重要影响的方法，并将确定干预措施可能对受影响儿童的社会发展产生最大影响的生命周期。