Genetics of Brain Structure and Function

大脑结构和功能的遗传学

基本信息

批准号：
7269416
负责人：
John Blangero
金额：
$ 53.73万
依托单位：
TEXAS BIOMEDICAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7269416
关键词：
Affect Anatomy Anxiety Disorders Architecture Attention deficit hyperactivity disorder Autistic Disorder Base of the Brain Biocompatible Materials Bioinformatics Biological Biology Biomedical Research Brain Brain Diseases Brain imaging Candidate Disease Gene Chromosome Mapping Communities Complex Computer Simulation DNA Resequencing Data Data Correlations Dementia Development Diabetes Mellitus Disease Disruption Dissection Economic Burden Epilepsy Evaluation Exhibits Extended Family Facility Construction Funding Category Family Foundations Foxes Funding Future Gene Expression Genes Genetic Genetic Determinism Genetic Polymorphism Genetic Research Genome Genome Scan Genomics Genotype Goals Health Sciences Heart Diseases Heritability Human Human Genetics Individual Individual Differences Intervention Joints Lead Leukocytes Link Localized Magnetic Resonance Imaging Measurable Measurement Measures Mental disorders Methods Mexican Americans Mission Modeling Molecular Analysis Mood Disorders Morbidity - disease rate National Institute of Mental Health Neurocognitive Neurologic Neurosciences Noise Nucleotides Numbers Osteoporosis Participant Pathology Phenotype Positioning Attribute Procedures Psyche structure Public Health Qualifying Quantitative Genetics Quantitative Trait Loci Rate Relative (related person)Research Research Design Research Personnel Resource Sharing Resources Reverse Transcriptase Polymerase Chain Reaction Risk Sampling Schizophrenia Short Tandem Repeat Signal Transduction Single Nucleotide Polymorphism Source Structure Susceptibility Gene Testing Texas Therapeutic Uncertainty Universities Variant addiction affection base cost effective disorder risk endophenotype gene discovery genetic analysis genetic pedigree genetic resource genome-wide linkage improved in vivo indexing member mortality neuroimaging neuropsychological novel novel diagnostics programs research study trait transcriptomics

项目摘要

DESCRIPTION (provided by applicant): The goal of this project is to identify quantitative trait loci associated with variation in brain structure and function. The ultimate promise of this research is the discovery of genes that predispose to brain disorders and mental illnesses. We believe that the analysis of genetic influences on brain structure and function in randomly sampled extended pedigrees will provide significant clues regarding the genes that are involved in both normal and pathological brain function. The focus of the project is on the genetic dissection of quantitative endophenotypes that more directly index the underlying biological basis of brain function than do discrete disease states themselves. To this end, we will perform neuroimaging and conduct neuropsychological examinations on Mexican American individuals who have been part of our ongoing genetic research studies for the past 15 years. All participants were previously genotyped and our plan is to utilize existing genome scan and genome-wide quantitative transcriptomic data for correlation with neuroanatomic and neurocognitive variables. Our specific aims are to: 1) perform high quality brain magnetic resonance imaging and neuropsychological examinations on 1,000 Mexican Americans who are members of approximately 30 large extended families, 2) assess the quantitative genetic architecture of brain-related phenotypes by estimating their heritabilities and their genetic correlations, 3) classify specific brain morphological variables and quantitative leukocyte-derived gene expression measures as endophenotypes related to brain function, 4) localize QTLs influencing variation in the quantitative brain-related phenotypes by performing linkage-based genome scanning using the variance component method, 5) refine the position of localized QTLs and identify positional candidate loci using an objective prioritization strategy that jointly utilizes in silico bioinformatics, genetic, and transcriptional data, and 6) identify the most likely functional variations within the two best positional candidate genes. This project involves coordinated R01 applications from Dr. John Blangero, Southwest Foundation for Biomedical Research, and Drs. David Glahn and Peter Fox, University of Texas Health Science Center at San Antonio. If funded, our data and biomaterials will be incorporated into the NIMH Human Genetics Initiative making them available to qualified researchers in the wider scientific community. Relevance to agency mission: Brain-related mental diseases are a major public health burden whose biology is still largely unknown. By identifying genes involved in brain function and structure, we will provide novel biological candidates for the determinants of such diseases and thus improve potential for intervention.

描述（由申请人提供）：该项目的目的是确定与大脑结构和功能变化相关的定量性状基因座。这项研究的最终希望是发现易感脑疾病和精神疾病的基因。我们认为，对随机采样扩展的分子的遗传影响对大脑结构和功能的分析将提供有关正常和病理脑功能涉及的基因的重要线索。该项目的重点是与离散疾病状态本身更直接地索引脑功能的基本生物学基础的定量内表型的遗传解剖。为此，我们将对过去15年来一直是我们正在进行的基因研究的一部分的墨西哥裔美国人进行神经影像学检查。所有参与者先前都是基因型的，我们的计划是利用现有的基因组扫描和全基因组定量转录组数据与神经解剖学和神经认知变量的相关性。我们的具体目的是：1）对1000名墨西哥裔美国人进行高质量的大脑磁共振成像和神经心理学检查，他们是大约30个大家庭的成员，2）评估与脑相关表型的定量遗传结构，通过估计其遗传性及其遗传相关性，3）分类的特定脑形态和数量的遗传学量，3） endophenotypes related to brain function, 4) localize QTLs influencing variation in the quantitative brain-related phenotypes by performing linkage-based genome scanning using the variance component method, 5) refine the position of localized QTLs and identify positional candidate loci using an objective prioritization strategy that jointly utilizes in silico bioinformatics, genetic, and transcriptional data, and 6) identify the most likely两个最佳位置候选基因中的功能变化。该项目涉及西南生物医学研究基金会和博士的John Blangero博士的协调R01申请。德克萨斯大学健康科学中心的David Glahn和Peter Fox。如果资助，我们的数据和生物材料将被纳入NIMH人类遗传学计划中，从而将其提供给更广泛的科学界的合格研究人员。与代理任务的相关性：与大脑相关的精神疾病是一种主要的公共卫生负担，其生物学仍然在很大程度上未知。通过鉴定涉及大脑功能和结构的基因，我们将为此类疾病的决定因素提供新颖的生物学候选物，从而提高干预潜力。