Network Based Approach to Gene Prioritization at Genome-Wide Association Study Loci

Abstract

Motivation: Genome-wide association studies (GWAS) have successfully identified thousands of genetic risk loci for complex traits and diseases. Most of these GWAS loci lie in regulatory regions of the genome and the gene through which each GWAS risk locus exerts its effects is not always clear. Many computational methods utilizing biological data sources have been proposed to identify putative casual genes at GWAS loci; however, these methods can be improved upon. Results: We present the Relations-Maximization Method, a dense module searching method to identify putative causal genes at GWAS loci through the generation of candidate sub-networks derived by integrating association signals from GWAS data into the gene co-regulation network. We employ our method in a chronic obstructive pulmonary disease GWAS. We perform an extensive, comparative study of Relations-Maximization Method's performance against well-established baselines.