Autistic Traits: Life Course & Genetic Structure

自闭症特征：生命历程

• 批准号: 8303302
• 负责人: JOHN N. CONSTANTINO
• 金额: $ 53.11万
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8303302
• 关键词: 11p; Accounting; Adolescence; Adolescent; Adult; Affect; African American; Age; Architecture; Asperger Syndrome; Attention deficit hyperactivity disorder; Autistic Disorder; Behavior; Behavioral; Biocompatible Materials; Biological Psychiatry; Brothers; Candidate Disease Gene; Caucasians; Caucasoid Race; Characteristics; Child; Childhood; 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; Health; Hispanics; Impaired cognition; Impairment; Incidence; Individual; Infant; Intervention; Interview; Life; Life Cycle Stages; 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; 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）：这是一项为期5年的竞争延续的申请，即对兄弟姐妹对自闭症社会障碍的持续纵向研究（R01）。鉴于关于自闭症的遗传和神经生物学结构的最新发现，很明显，自闭症现象的可遗传定量成分的更精确表征可能会加速发现自闭症特定遗传和神经生物学原因。这项研究将涉及5576名受试者的定量表型（来自有或没有自闭症谱系障碍的儿童的1295个临床确定的家族（ASD）。它将包括：评估父母和受影响的个体的评估和受影响的人的延长的家族；检查是否具有各种自动化的家族的定量自动化特征的模式是其他自动化，善良，简单繁殖，Versus vers vers vers vers vers vers vers vers vers'''''表型的协变量；对现有的纵向研究对象，可以更好地阐明自闭症社会障碍的发展过程； 新型定量内表型（运动，体感和电生理学）的同胞可能与自闭症社会障碍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。在此应用程序中，我们试图回应以前对自闭症的家庭遗传研究的问题，通常代表性的少数群体和处境不利的人群，在现有的研究和数据集中，对自闭症的特定责任（如果存在）。除了这项大型临床确定的同胞样本的表型表征增强外，其中有475个家族将通过两项正在进行的自闭症国家链接研究（自闭症基因资源交换和Simons Simplex Collection）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，研究结果还将增强衡量治疗微妙影响的方法，当干预措施可能对社会发展产生特殊影响时，将确定寿命的间隔，并将阐明在包括非ASD儿童的范围内（包括AD-ASD范围）的功能残疾，包括AD-ASD的范围是广泛的（包括AD）的范围（ 亚临床自闭症特征的同时出现。公共卫生相关性：自闭症和相关疾病会影响美国每150名儿童中有1个，并在一生中造成严重的社会障碍。这项研究研究了自闭症社会障碍在整个过程中的变化 童年时期，它们是如何跨几代传播的，以及它们破坏了哪些正常的发展过程。该研究的结果将有助于搜索引起自闭症的基因和神经异常，将增强衡量干预的微妙但重要影响的方法，并在干预措施可能对受影响儿童的社会发展产生最大影响时确定寿命的间隔。

项目成果

On the Continuity Between Autistic and Schizoid Personality Disorder Trait Burden: A Prospective Study in Adolescence.

关于自闭症和分裂样人格障碍特质负担之间的连续性：青春期的前瞻性研究。

• DOI: 10.1097/nmd.0000000000001105
• 发表时间: 2020
• 期刊: The Journal of nervous and mental disease
• 作者: Cook,MichalLauren;Zhang,Yi;Constantino,JohnN
• 通讯作者: Constantino,JohnN

Sibling recurrence and the genetic epidemiology of autism.

• DOI: 10.1176/appi.ajp.2010.09101470
• 发表时间: 2010-11
• 期刊: The American journal of psychiatry
• 作者: Constantino JN;Zhang Y;Frazier T;Abbacchi AM;Law P
• 通讯作者: Law P

Evidence for shared genetic influences on self-reported ADHD and autistic symptoms in young adult Australian twins.

• DOI: 10.1375/twin.11.6.579
• 发表时间: 2008-12
• 期刊: Twin research and human genetics : the official journal of the International Society for Twin Studies
• 作者: Reiersen AM;Constantino JN;Grimmer M;Martin NG;Todd RD
• 通讯作者: Todd RD

Multi-informant ratings of psychiatric symptom severity in children with autism spectrum disorders: the importance of environmental context.

• DOI: 10.1007/s10803-009-0694-7
• 发表时间: 2009-06
• 期刊: JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
• 影响因子: 3.9
• 作者: Kanne, Stephen M.;Abbacchi, Anna M.;Constantino, John N.
• 通讯作者: Constantino, John N.

Developmental course of autistic social impairment in males.

• DOI: 10.1017/s095457940900008x
• 发表时间: 2009
• 期刊: DEVELOPMENT AND PSYCHOPATHOLOGY
• 影响因子: 3.3
• 作者: Constantino, John N.;Abbacchi, Anna M.;Lavesser, Patricia D.;Reed, Hannah;Givens, Leah;Chiang, Lily;Gray, Teddi;Gross, Maggie;Zhang, Yi;Todd, Richard D.
• 通讯作者: Todd, Richard D.