Genetic influences on the brain: A twin imaging study

遗传对大脑的影响：双胞胎成像研究

基本信息

批准号：
7627350
负责人：
Margaret Jane WRIGHT
金额：
$ 50.9万
依托单位：
QUEENSLAND INSTITUTE OF MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7627350
关键词：
Accounting Affect Age Agreement Alleles Anatomy Anterior Apolipoprotein E Architecture Area Arts Back Behavior Behavioral Bilateral Biological Biological Neural Networks Biology Brain Brain Diseases Brain Mapping Brain imaging Brain region Brain-Derived Neurotrophic Factor Brodmann&apos s area Candidate Disease Gene Chromosomes, Human, Pair 4 Clinical Research Cognitive Complex Corpus Callosum Cost Savings Coupling Development Diffusion Diffusion Magnetic Resonance Imaging Disease Dopamine Employment Environment Environmental Risk Factor Episodic memory Equation Etiology Fiber Foundations Frontal gyrus Functional Imaging Functional Magnetic Resonance Imaging Funding Future Genes Genetic Genetic Markers Genetic Models Genetic Polymorphism Genetic Variation Genome Genotype Gray unit of radiation dose Heritability Hippocampal Formation Hippocampus (Brain)Histocompatibility Testing Human Image Individual Individual Differences Inferior Insula of Reil Investigation Knowledge Laboratories Language Link Literature Lobule Magnetic Resonance Imaging Maps Measures Mediation Mental disorders Methods Microcephaly Modeling Myelin Nature Neuregulins Neurologic Neurons Parietal Parietal Lobe Pattern Performance Phenotype Prefrontal Cortex Procedures Process Proxy Psychometrics Quantitative Trait Loci Queensland RHOA gene Reaction Time Regulation Relative (related person)Resources Role Sampling Scanning Schizophrenia Series Short-Term Memory Siblings Specificity Structure System Techniques Temporal Lobe Testing Time Tissues Twin Multiple Birth Universities Variant Visuospatial Work age related aged apolipoprotein E-4 base brain shape brain size brain tissue brain volume cognitive function cost effective density design developmental disease expectation frontal lobe genetic analysis genetic association genetic linkage analysis genetic profiling genome wide association study genome-wide linkage gray matter insight interest meetings morphometry myelination neuroimaging neuropsychological non-genetic novel processing speed regional difference relating to nervous system valylvaline white matter

项目摘要

DESCRIPTION (provided by applicant): There is great individual variation in the structure and function of the brain. Discovering the determinants of this variation will not only advance our knowledge of normal brain development, but further our understanding of developmental disorders and diseases that affect the brain. The long-term objective of this application is to characterize the differential roles of genes and environment in shaping brain structure and function, to map and identify the genes involved, and to characterize the impact of brain relevant genetic polymorphisms. We shall collect structural images on a genetically informative sample of 700 Australian twins and their non-twin singleton siblings (aged 20-26 yrs) from whom we have previously obtained measures of cognitive functioning, and for whom we have extensive genotyping already available. Using state-of-the-art brain mapping techniques we will establish the genetic architecture and show the trajectory of genetic effects on brain morphometry (Specific Aim 1). In addition to structural MRI, twins and their siblings will participate in diffusion tensor (DTI) (Specific Aim 2) and functional (fMRI) imaging (Specific Aim 3). Our brain mapping techniques will be extended, for the first time, to model genetic and non-genetic influences on white matter micro-structure, and to reveal the genetic topography. The functional imaging study will apply the widely used 'N-back' working memory task, since this is the process most directly linked to individual differences in cognitive ability. We shall assess the extent of genetic mediation and generate the first detailed heritability maps of neuronal activity during working memory. Multivariate genetic modeling of twin/sibling covariance will be used to estimate the relative contributions of genetic factors to co-variance between regional brain structures, areas of working memory-related brain activation, and cognitive ability (Specific Aim 4). Genome-wide linkage and association scans (funded elsewhere) will be used to identify genetic loci that contribute to heritability of brain morphometry and functioning (Specific Aim 5). We will also screen three brain relevant genetic polymorphisms for affects on selected neural phenotypes using sib-pair allelic association analysis (Specific Aim 6). No other imaging study in twins has been designed specifically to use such a QTL-mapping strategy, and this will be at marked cost savings due to the employment of an existing well-genotyped sample. A final aim is to provide a unique and valuable resource base for future investigation (Specific Aim 7). The results of this study will provide fundamental information on genetic mechanisms influencing variation in brain structure and function. This will provide new insights into the origin of individual differences in cognitive functioning and vulnerability to brain disorders.

描述（由申请人提供）：大脑的结构和功能存在很大的个人变化。发现这种变化的决定因素不仅会促进我们对正常大脑发育的了解，还可以进一步了解我们对影响大脑的发育障碍和疾病的理解。该应用的长期目标是表征基因和环境在塑造大脑结构和功能，绘制和识别所涉及的基因的差异作用，并表征大脑相关的遗传多态性的影响。我们将收集700个澳大利亚双胞胎及其非双胞胎单身兄弟姐妹（20 - 26岁）的遗传信息样本上的结构图像，我们以前从中获得了认知功能的量度，并且我们已经获得了广泛的基因分型。使用最先进的脑图技术，我们将建立遗传结构，并显示遗传对脑形态计量学的轨迹（特定目标1）。除结构MRI外，双胞胎及其兄弟姐妹还将参与扩散张量（DTI）（特定目标2）和功能（fMRI）成像（特定目标3）。我们的大脑映射技术将首次扩展，以模拟对白质微结构的遗传和非遗传影响，并揭示遗传形态。功能成像研究将应用广泛使用的“ n背”工作记忆任务，因为这是与认知能力中个体差异最直接相关的过程。我们将评估遗传介导的程度，并在工作记忆过程中产生第一个详细的神经元活动遗传图。双/兄弟姐妹协方差的多元遗传模型将用于估计遗传因素对区域大脑结构之间的共同变量，工作记忆相关的大脑激活和认知能力的相对贡献（特定目标4）。全基因组的联系和关联扫描（在其他地方资助）将用于识别有助于脑形态计量学和功能的遗传力的遗传基因座（特定目标5）。我们还将使用SIB-PAIR等位基因关联分析（特定目标6）筛选出三个大脑相关的遗传多态性，以对所选神经表型的影响。在双胞胎中没有其他设计的成像研究专门用于使用这种QTL映射策略，由于使用了现有良好的样本，这将以明显的成本节省。最终目的是为未来的调查提供独特而宝贵的资源基础（特定目标7）。这项研究的结果将提供有关影响大脑结构和功能变化的遗传机制的基本信息。这将为认知功能和脑部疾病脆弱性的个体差异的起源提供新的见解。