A Novel Three-Stage Framework for Association Analysis Between SNPs and Brain Regions

Abstract

Motivation: At present, a number of correlation analysis methods between SNPs and ROIs have been devised to explore the pathogenic mechanism of Alzheimer's disease. However, some of the deficiencies inherent in these methods, including lack of statistical efficacy and biological meaning. This study aims at addressing issues: insufficient correlation by previous methods (relative high regression error) and the lack of biological meaning in association analysis. Results: In this paper, a novel three-stage SNPs and ROIs correlation analysis framework is proposed. Firstly, clustering algorithm is applied to remove the potential linkage unbalanced structure of two SNPs. Then, the group sparse model is used to introduce prior information such as gene structure and linkage unbalanced structure to select feature SNPs. After the above steps, each SNP has a weight vector corresponding to each ROI, and the importance of SNPs can be judged according to the weights in the feature vector, and then the feature SNPs can be selected. Finally, for the selected feature SNPS, a support vector machine regression model is used to implement the prediction of the ROIs phenotype values. The experimental results under multiple performance measures show that the proposed method has better accuracy than other methods.

Keywords: Alzheimer's disease; association analysis; data mining; imaging genetics; single nucleotide polymorphism.