Mapping the Genetic-Imaging-Clinical Pathway with Applications to Alzheimer's Disease

• 成果类型: Article
• 署名作者: Yu, Dengdeng; Wang, Linbo; Kong, Dehan; Zhu, Hongtu
• 署名单位: University of Texas System; University of Texas Arlington; University of Toronto; University of North Carolina; University of North Carolina Chapel Hill
• 刊物名称: JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
• ISSN/ISSBN: 0162-1459
• DOI: 10.1080/01621459.2022.2087658
• 发表日期: 2022
• 页码: 1656-1668
• 关键词: whole-genome association; hippocampal atrophy; cognitive impairment; cerebrospinal-fluid; cholinergic system; hypothetical model; variable selection; haplotype blocks; amyloid-beta; tau

摘要

Alzheimer's disease is a progressive form of dementia that results in problems with memory, thinking, and behavior. It often starts with abnormal aggregation and deposition of beta amyloid and tau, followed by neuronal damage such as atrophy of the hippocampi, leading to Alzheimer's disease (AD). The aim of this article is to map the genetic-imaging-clinical pathway for AD in order to delineate the genetically-regulated brain changes that drive disease progression based on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. We develop a novel two-step approach to delineate the association between high-dimensional 2D hippocampal surface exposures and the Alzheimer's Disease Assessment Scale (ADAS) cognitive score, while taking into account the ultra-high dimensional clinical and genetic covariates at baseline. Analysis results suggest that the radial distance of each pixel of both hippocampi is negatively associated with the severity of behavioral deficits conditional on observed clinical and genetic covariates. These associations are stronger in Cornu Ammonis region 1 (CA1) and subiculum subregions compared to Cornu Ammonis region 2 (CA2) and Cornu Ammonis region 3 (CA3) subregions. for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.