Neural and Phenotypic Correlates of Autism Risk Genes

自闭症风险基因的神经和表型相关性

基本信息

批准号：
7844429
负责人：
SUSAN Y BOOKHEIMER
金额：
$ 54.51万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7844429
关键词：
22q 22q11.2 Alleles Amygdaloid structure Anxiety Area Autistic Disorder Behavior Behavioral Brain Brain region Child Cognitive deficits Complex Corpus striatum structure Data Development DiGeorge Syndrome Diagnostic Disease Dorsal Enrollment Eye Face Functional Imaging Functional Magnetic Resonance Imaging Gene Targeting Genes Genetic Genetic Polymorphism Genetic Risk Genetic Variation Genetic screening method Goals Grant Heterogeneity Hypersensitivity Image Impairment Incidence Inferior Inferior frontal gyrus Language Language Development Lead Learning Link Magnetic Resonance Imaging Maps Measures Medial Mediating Metric Mind Motor Mutation Parietal Parietal Lobe Pathway interactions Pattern Phenotype Prefrontal Cortex Recruitment Activity Rewards Risk Sampling Sensory Short-Term Memory Site Stimulus Structure Symptoms Syndrome System Triad Acrylic Resin Variant Work base cohort emotional stimulus endophenotype executive function frontal lobe gaze genetic analysis genetic risk factor genetic variant language onset mirror neuron morphometry public health relevance relating to nervous system response social social communication social reciprocity theories white matter

项目摘要

DESCRIPTION (provided by applicant): Autism is a tremendously heterogeneous disorder with complex genetic and neural underpinnings. This grant aims to understand variability in the autism phenotype by examining links between known genetic risk factors for autism and brain structure and function. We will recruit 80 children with autism and 40 controls who will undergo a comprehensive phenotyping assessment, high field structural MRI, and functional MRI using three tasks that differentiate typically developing children from those with autism, and which tap into core deficits seen in ASD. Our study will focus on five autism risk polymorphisms and one known genetic syndrome, 22q11deletiion with the goal of identifying structural and functional brain abnormalities that are linked to autism risk polymorphisms, and in turn to link these neural anomalies to variations in the autism phenotype. We hope to develop profiles of imaging phenotypes in autism that will help identify valid autism subtypes based on brain structure and function, and link these phenotypes to their genetic origins, thereby moving towards a more crystallized conceptualization of ASD. PUBLIC HEALTH RELEVANCE: This grant aims to examine the effects of 5 replicated autism risk genes on brain structure and function, using functional and structural MRI. The goal is to try to understand the neural basis of behavioral variations in autism by drawing connections from genes to brain to behavior. We will examine 5 autism risk genes and one known genetic syndrome, 22q11deltion, where there are high rates of autism, and identify brain regions and systems associated with these genes, relating them to variations in the autism phenotype.

描述（由申请人提供）：自闭症是一种具有复杂遗传和神经基础的异质性疾病。该赠款旨在通过检查自闭症与大脑结构和功能的已知遗传风险因素之间的联系来了解自闭症表型的变异性。我们将招募80名自闭症儿童和40个对照儿童，他们将使用三个任务，这些任务将通常与自闭症患者分开，并利用ASD中的核心缺陷。我们的研究将侧重于五种自闭症风险多态性和一种已知的遗传综合征，即22q11骨骼，其目的是识别与自闭症风险多态性有关的结构和功能性脑异常，进而将这些神经异常与自闭症现象中的变体联系起来。我们希望在自闭症中开发成像表型的概况，这将有助于基于大脑结构和功能识别有效的自闭症亚型，并将这些表型与它们的遗传起源联系起来，从而朝着更结晶的ASD概念化迈进。公共卫生相关性：该赠款旨在使用功能和结构MRI检查5种复制的自闭症风险基因对大脑结构和功能的影响。目的是尝试通过从基因到大脑到行为的联系来理解自闭症行为变化的神经基础。我们将检查5个自闭症风险基因和一种已知的遗传综合征，即22q11deltion，其中自闭症发生率很高，并确定与这些基因相关的大脑区域和系统，将它们与自闭症表型的变化有关。