Genetic study of Restricted Repetitive Behavior in Autism Spectrum Disorders

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）儿童异常重复行为（如拍打手臂，排列物体，对奇怪物体的特殊迷恋，非常狭窄的限制兴趣，以及对常规变化的不耐受）的遗传因素。限制性重复行为（RRB）作为asd的核心特征之一，经常主导患儿的日常活动，干扰其发展功能行为的机会，需要干预和治疗。尽管RRB具有临床意义，但对其潜在的遗传机制知之甚少。在本研究中，我们拟在既往研究表明GABA和谷氨酸神经传递异常参与RRB和asd发病机制的基础上，探讨GABA和谷氨酸神经传递系统的遗传变异是否在asd儿童RRB发病机制中发挥作用。我们将通过一个以社区为基础的支持组织，为有自闭症儿童的学校和家庭寻找年龄在6到18岁之间的儿童。被确诊儿童的主要照顾者将被要求完成一系列的评定量表，包括社会沟通量表（SCQ）、社会反应量表（SRS）、重复行为量表修订版（rb -r）、Vineland适应行为量表- ii（家长/照顾者评定表）以及药物、家族精神病史和既往病史问卷。同意的儿童将被要求捐献唾液或口腔拭子样本进行基因分型。研究人员将对大约750个GABA和谷氨酸系统相关基因的单核苷酸多态性（snp）进行基因分型，并分析特定遗传变异与RRB特定形式之间的定量关联。此外，我们将在GABA和谷氨酸系统相关基因中确定对RRB数量性状有上位性贡献的位点作为次要目标。如果RRB的遗传基础被确定，这将导致对这种慢性和破坏性疾病的早期发现和治疗的新见解。公共卫生相关性：我们的目标是发现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不适应重复行为的发展中起关键作用。积极的发现可能会导致对这种慢性致残疾病的早期发现和治疗的新见解。

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.