Deep-gated recurrent unit and diet network-based genome-wide association analysis for detecting the biomarkers of Alzheimer's disease.

ABSTRACT

Genome-wide association analysis (GWAS) is a commonly used method to detect the potential biomarkers of Alzheimer's disease (AD). Most existing GWAS methods entail a high computational cost, disregard correlations among imaging data and correlations among genetic data, and ignore various associations between longitudinal imaging and genetic data. A novel GWAS method was proposed to identify potential AD biomarkers and address these problems. A network based on a gated recurrent unit was applied without imputing incomplete longitudinal imaging data to integrate the longitudinal data of variable lengths and extract an image representation. In this study, a modified diet network that can considerably reduce the number of parameters in the genetic network was proposed to perform GWAS between image representation and genetic data. Genetic representation can be extracted in this way. A link between genetic representation and AD was established to detect potential AD biomarkers. The proposed method was tested on a set of simulated data and a real AD dataset. Results of the simulated data showed that the proposed method can accurately detect relevant biomarkers. Moreover, the results of real AD dataset showed that the proposed method can detect some new risk-related genes of AD. Based on previous reports, no research has incorporated a deep-learning model into a GWAS framework to investigate the potential information on super-high-dimensional genetic data and longitudinal imaging data and create a link between imaging genetics and AD for detecting potential AD biomarkers. Therefore, the proposed method may provide new insights into the underlying pathological mechanism of AD.