Genome-Wide Prioritization of Disease Genes and Identification of Disease-Disease Associations from an Integrated Human Functional Linkage Network

Abstract

An evidence-weighted functional-linkage network of human genes reveals associations among diseases that share no known disease genes and have dissimilar phenotypes. We integrate 16 genomic features to construct an evidence-weighted functional-linkage network comprising 21,657 human genes. The functional-linkage network is used to prioritize candidate genes for 110 diseases, and to reliably disclose hidden associations between disease pairs having dissimilar phenotypes, such as hypercholesterolemia and Alzheimer's disease. Many of these disease-disease associations are supported by epidemiology, but with no previous genetic basis. Such associations can drive novel hypotheses on molecular mechanisms of diseases and therapies.