Association Discovery and Diagnosis of Alzheimer’s Disease with Bayesian Multiview Learning

Abstract

The analysis and diagnosis of Alzheimers disease (AD) can be based on genetic variations, e.g., single nucleotide polymorphisms (SNPs) and phenotypic traits, e.g., Magnetic Resonance Imaging (MRI) features. We consider two important and related tasks: i) to select genetic and phenotypical markers for AD diagnosis and ii) to identify associations between genetic and phenotypical data. While previous studies treat these two tasks separately, they are tightly coupled because underlying associations between genetic variations and phenotypical features contain the biological basis for a disease. Here we present a new sparse Bayesian approach for joint association study and disease diagnosis. In this approach, common latent features are extracted from different data sources based on sparse projection matrices and used to predict multiple disease severity levels; in return, the disease status can guide the discovery of relationships between data sources. The sparse projection matrices not only reveal interactions between data sources but also select groups of biomarkers related to the disease. Moreover, to take advantage of the linkage disequilibrium (LD) measuring the non-random association of alleles, we incorporate a graph Laplacian type of prior in the model. To learn the model from data, we develop an efficient variational inference algorithm. Analysis on an imaging genetics dataset for the study of Alzheimers Disease (AD) indicates that our model identifies biologically meaningful associations between genetic variations and MRI features, and achieves significantly higher accuracy for predicting ordinal AD stages than the competing methods.