Imaging and Genetics in Huntington's Disease

亨廷顿病的影像学和遗传学

基本信息

批准号：
8596213
负责人：
VINCE D CALHOUN
金额：
$ 47.25万
依托单位：
THE MIND RESEARCH NETWORK
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-15 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8596213
关键词：
Acceleration Accounting Activities of Daily Living Age Age of Onset Alzheimer&apos s Disease Ancillary Study Brain Brain imaging CAG repeat Candidate Disease Gene Clinical Cognitive Corpus striatum structure Data Data Collection Data Set Diagnosis Disease Disease Progression Educational workshop Ensure Fingerprint Genes Genetic Genetic Markers Genetic Variation Genome Genotype Human Resources Huntington Disease Huntington gene Image Impaired cognition Individual Informatics Lead Measures Methods Motor Onset of illness Other Genetics Parents Pathway interactions Pattern Persons Phase Phenotype Process Research Infrastructure Sampling Scanning Schizophrenia Signal Pathway Single Nucleotide Polymorphism Site Structure Symptoms System Techniques Time Training Trinucleotide Repeats Uncertainty Variant Work base brain volume clinical Diagnosis cognitive function data management disorder control functional decline genetic analysis genetic profiling gray matter human Huntingtin protein independent component analysis loss of function meetings motor control prospective public health relevance resilience white matter

项目摘要

DESCRIPTION (provided by applicant): The PREDICT-HD study has collected an impressive sample of healthy subjects with the marker for Huntington's Disease (HD), and a sample of controls without that marker. The analyses of cognitive, psychiatric, and motor function over time in this sample has provided evidence for a prodromal phase preceding clinical diagnosis of HD: In many of the domains being measured, subjects who are more than 15 years away from their predicted age of onset show little or no difference from controls, while subjects in the 9- 1 year window are already showing significant if subtle declines, and within 9 years of the predicted age of onset are showing large losses. While this is an impactful clarification of the prodromal phase of HD, it needs to be further clarified; the predicted age of onset as calculated by the number of CAG repeats in the Huntington gene is very precise when the number of repeats is high, but can lead to a very large window of several decades when the number is low. In this ancillary study, we apply multivariate techniques such as parallel independent components analysis (pICA) to the combined structural and genetic imaging data from the PREDICT sample. In Aim 1, using a cross-sectional technique we will identify the genetic profiles which covary with disease-related patterns of gray matter loss. In Aim 2, using a longitudinal sample we will identify the brain structure and genetic profiles which correlate with loss of motor and cognitive function. In Aim 3, we will ensure that the PREDICT team is trained on these techniques and can apply them to its ongoing data collection, and that the results are incorporated into their data management system. The conclusion of this proposal places the effect of the CAG repeats within an initial context of genetic influences from the larger genome. We leverage the brain imaging measures to identify relevant profiles of genotypes within the HTT genetic network which accelerate or provide resilience to disease onset.

描述（由申请人提供）：预测HD研究已收集了具有亨廷顿疾病标记（HD）标记的健康受试者的令人印象深刻的样本，以及没有该标记的对照样本。该样本中对认知，精神病学和运动功能的分析提供了在高清临床诊断之前先于前阶段的证据：在许多正在测量的领域中，距离预测的年龄相距15年以上的受试者在9--1年窗口中的受试者在较大的范围内显示出了9年的损失，并且在9-1年中显示出了9年的损失，并且在9-1年中显示出了9年的损失，并且在9-1年中显示出9年的损失。尽管这是对高清前驱阶段的有影响力的澄清，但需要进一步阐明。当重复次数较高时，由亨廷顿基因中CAG重复序列的数量计算出的预测年龄非常精确，但是当数量较低时，几十年来可能会导致很大的窗口。在这项辅助研究中，我们将多元技术（例如平行独立组件分析（PICA））应用于预测样本的结构和遗传成像数据。在AIM 1中，使用横截面技术，我们将确定与与疾病相关的灰质损失模式相关的遗传特征。在AIM 2中，使用纵向样本，我们将确定与运动和认知功能丧失相关的大脑结构和遗传特征。在AIM 3中，我们将确保对预测团队进行这些技术的培训，并可以将其应用于其正在进行的数据收集，并将结果纳入其数据管理系统。该提案的结论将CAG重复的效果置于较大基因组遗传影响的初始背景下。我们利用大脑成像措施来确定HTT遗传网络中基因型的相关曲线，该基因型在加速或为疾病发作提供韧性。