Network-Based Genome Wide Study of Hippocampal Imaging Phenotype In Alzheimer's Disease To Identify Functional Interaction Modules

Abstract

Identification of functional modules from biological network is a promising approach to enhance the statistical power of genome-wide association study (GWAS) and improve biological interpretation for complex diseases. The precise functions of genes are highly relevant to tissue context, while a majority of module identification studies are based on tissue-free biological networks that lacks phenotypic specificity. In this study, we propose a module identification method that maps the GWAS results of an imaging phenotype onto the corresponding tissue-specific functional interaction network by applying a machine learning framework. Ridge regression and support vector machine (SVM) models are constructed to re-prioritize GWAS results, followed by exploring hippocampus-relevant modules based on top predictions using GWAS top findings. We also propose a GWAS top-neighbor-based module identification approach and compare it with Ridge and SVM based approaches. Modules conserving both tissue specificity and GWAS discoveries are identified, showing the promise of the proposal method for providing insight into the mechanism of complex diseases