Imaging Genetics Study Based on a Temporal Group Sparse Regression and Additive Model for Biomarker Detection of Alzheimer's Disease.

Abstract

Imaging genetics is an effective tool used to detect potential biomarkers of Alzheimer's disease (AD) in imaging and genetic data. Most existing imaging genetics methods analyze the association between brain imaging quantitative traits (QTs) and genetic data [e.g., single nucleotide polymorphism (SNP)] by using a linear model, ignoring correlations between a set of QTs and SNP groups, and disregarding the varied associations between longitudinal imaging QTs and SNPs. To solve these problems, we propose a novel temporal group sparsity regression and additive model (T-GSRAM) to identify associations between longitudinal imaging QTs and SNPs for detection of potential AD biomarkers. We first construct a nonparametric regression model to analyze the nonlinear association between QTs and SNPs, which can accurately model the complex influence of SNPs on QTs. We then use longitudinal QTs to identify the trajectory of imaging genetic patterns over time. Moreover, the SNP information of group and individual levels are incorporated into the proposed method to boost the power of biomarker detection. Finally, we propose an efficient algorithm to solve the whole T-GSRAM model. We evaluated our method using simulation data and real data obtained from AD neuroimaging initiative. Experimental results show that our proposed method outperforms several state-of-the-art methods in terms of the receiver operating characteristic curves and area under the curve. Moreover, the detection of AD-related genes and QTs has been confirmed in previous studies, thereby further verifying the effectiveness of our approach and helping understand the genetic basis over time during disease progression.