论文标题

用于整合遗传,成像和临床数据的部分功能线性建模框架

A Partially Functional Linear Modeling Framework for Integrating Genetic, Imaging, and Clinical Data

论文作者

Li, Ting, Yu, Yang, Marron, J. S., Zhu, Hongtu

论文摘要

本文是由对阿尔茨海默氏病神经成像计划(ADNI)研究中收集的遗传,成像和临床(GIC)数据的联合分析进行的。我们提出了一个基于部分功能性线性回归模型的回归框架,以绘制阿尔茨海默氏病(AD)的高维GIC相关途径。我们通过将成像数据嵌入重现Hilbert空间并施加遗传变量系数的L0惩罚来开发联合模型选择和估计程序。我们将提出的方法应用于ADNI数据集,以鉴定成千上万的遗传多态性(使用预处理步骤减少数百万的遗传多态性),并研究一套有益的遗传变异和基线海马表面对未来的认知能力的一组遗传变异的影响。我们探索这些认知得分的共同和不同的遗传力模式。分析结果表明,海马和遗传数据都对不同分数都有异质作用,其趋势是两种海马的价值与认知缺陷的严重程度负相关。所有13个认知评分都观察到多基因效应。著名的APOE4基因型仅解释了认知功能的一小部分。然而,在考虑基线诊断状态后,疾病分类中存在更大的遗传异质性。这些分析可用于进一步研究AD进化的功能机制。

This paper is motivated by the joint analysis of genetic, imaging, and clinical (GIC) data collected in the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. We propose a regression framework based on partially functional linear regression models to map high-dimensional GIC-related pathways for Alzheimer's Disease (AD). We develop a joint model selection and estimation procedure by embedding imaging data in the reproducing kernel Hilbert space and imposing the L0 penalty for the coefficients of genetic variables. We apply the proposed method to the ADNI dataset to identify important features from tens of thousands of genetic polymorphisms (reduced from millions using a preprocessing step) and study the effects of a certain set of informative genetic variants and the baseline hippocampus surface on thirteen future cognitive scores measuring different aspects of cognitive function. We explore the shared and different heritability patterns of these cognitive scores. Analysis results suggest that both the hippocampal and genetic data have heterogeneous effects on different scores, with the trend that the value of both hippocampi is negatively associated with the severity of cognition deficits. Polygenic effects are observed for all thirteen cognitive scores. The well-known APOE4 genotype only explains a small part of cognitive function. Shared genetic etiology exists, however, greater genetic heterogeneity exists within disease classifications after accounting for the baseline diagnosis status. These analyses are useful in further investigation of functional mechanisms for AD evolution.

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