Genetic study of Restricted Repetitive Behavior in Autism Spectrum Disorders

自闭症谱系障碍限制性重复行为的遗传学研究

• 批准号: 7686255
• 负责人: Soo-Jeong Kim
• 金额: $ 7.29万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-11 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7686255
• 关键词: Adaptive Behaviors; Affect; Age; Alleles; Area; Autistic Disorder; Basal Ganglia; Behavior; Biochemical; Caregivers; Characteristics; Child; Chronic; Clinical; Communication; Communities; Complex; Consent; DNA; Development; Disease; Early Diagnosis; Family; Florida; Functional disorder; Genes; Genetic; Genetic Epistasis; Genetic Variation; Genotype; Glutamates; Goals; Haplotypes; Hereditary Disease; Impairment; Intervention; Lead; Link; Measures; Mediating; Medical History; Methods; Molecular Genetics; Neuraxis; Neurons; Neurotransmitters; Oligogenic Traits; Parents; Pathogenesis; Pathway interactions; Pharmaceutical Preparations; Phenotype; Play; Predisposition; Questionnaires; Reciprocal Social Interaction; Recording of previous events; Recruitment Activity; Role; Saliva; Sampling; Schools; Single Nucleotide Polymorphism; Surgical Flaps; Susceptibility Gene; Swab; Symptoms; System; Testing; Universities; Upper arm; autism spectrum disorder; base; clinically significant; disability; gamma-Aminobutyric Acid; gene interaction; genetic variant; insight; interest; migration; neuroimaging; neurotransmission; programs; public health relevance; social; social communication; trait

DESCRIPTION (provided by applicant): The objective of this study is to identify contributing genetic factors for abnormal repetitive behavior (such as flapping arms, lining up objects, peculiar fascination with odd objects, a very narrow restricted interest, and intolerance to changes of routines) among children with autism spectrum disorders (ASDs). As one of the core features of ASDs, restricted repetitive behavior (RRB) frequently dominates the daily activities of affected children, interferes with opportunities to develop functional behaviors, and requires intervention and treatment. Despite the clinical significance of RRB, little is known about underlying genetic mechanisms. In this study, we propose to investigate whether genetic variations within the GABA and glutamate neurotransmission system play a role in the pathogenesis of RRB in children with ASDs, based on prior studies implicating abnormal GABA and glutamate neurotransmission in the pathogeneses of RRB as well as ASDs. We will identify children between ages of 6 and 18 through a community-based support organization for schools and families with children with ASDs. The primary caregivers of the identified children will be asked to complete a battery of rating scales including the social communication questionnaire (SCQ), social responsiveness scale (SRS), the repetitive behavior scale-revised (RBS-R), the Vineland Adaptive Behavior Scale-II (parent/caregiver rating form) and a questionnaire for medication, family psychiatric history and past medical history. Consenting children will be asked to donate either saliva or buccal swab samples for genotyping. A total of ~750 single nucleotide polymorphisms (SNPs) from the GABA and glutamate system related genes will be genotyped and analyzed for quantitative association between specific genetic variants and specific forms of RRB. In addition, we will identify loci contributing epistatically to quantitative traits of RRB among the GABA and glutamate system related genes as a secondary aim. If genetic underpinnings of RRB are identified, this will lead to new insight as to early detection and treatment of this chronic and devastating condition. PUBLIC HEALTH RELEVANCE: Our goal is to find contributing genetic factors for abnormal repetitive behavior among children with autism spectrum disorders. We hypothesize that genes related to the GABA and glutamate neurotransmission system may play a key role in the development of the maladaptive repetitive behavior. Positive findings may lead to a new insight as to early detection and treatment of this chronic and disabling condition.

描述（由申请人提供）：本研究的目的是确定自闭症谱系障碍（ASD）儿童中异常重复行为（例如拍打手臂、排列物体、对奇怪物体的特殊迷恋、非常狭窄的有限兴趣以及不能容忍日常生活改变）的遗传因素。作为 ASD 的核心特征之一，受限重复行为 (RRB) 经常主导受影响儿童的日常活动，干扰发展功能性行为的机会，需要干预和治疗。尽管 RRB 具有临床意义，但人们对潜在的遗传机制知之甚少。在这项研究中，我们基于之前的研究表明，GABA 和谷氨酸神经传递系统内的遗传变异是否在 ASD 儿童 RRB 的发病机制中发挥作用，研究表明异常的 GABA 和谷氨酸神经传递系统与 RRB 和 ASD 的发病机制有关。我们将通过社区支持组织为有 ASD 儿童的学校和家庭识别 6 岁至 18 岁之间的儿童。已确定儿童的主要照顾者将被要求填写一系列评级量表，包括社会沟通问卷（SCQ）、社会反应量表（SRS）、重复行为量表修订版（RBS-R）、瓦恩兰适应性行为量表-II（家长/照顾者评级表）以及药物、家庭精神病史和既往病史调查问卷。同意的儿童将被要求捐赠唾液或口腔拭子样本进行基因分型。来自 GABA 和谷氨酸系统相关基因的总共约 750 个单核苷酸多态性 (SNP) 将被进行基因分型并分析特定遗传变异与特定形式的 RRB 之间的定量关联。此外，我们将确定 GABA 和谷氨酸系统相关基因中对 RRB 数量性状有上位贡献的位点作为次要目标。如果 RRB 的遗传基础得到确定，这将为这种慢性破坏性疾病的早期发现和治疗带来新的见解。公共健康相关性：我们的目标是找到导致自闭症谱系障碍儿童异常重复行为的遗传因素。我们假设与 GABA 和谷氨酸神经传递系统相关的基因可能在适应不良重复行为的发展中发挥关键作用。积极的发现可能会让我们对这种慢性致残性疾病的早期发现和治疗产生新的认识。