GWAB: a web server for the network-based boosting of human genome-wide association data

Nucleic Acids Res. 2017 Jul 3;45(W1):W154-W161. doi: 10.1093/nar/gkx284.

Abstract

During the last decade, genome-wide association studies (GWAS) have represented a major approach to dissect complex human genetic diseases. Due in part to limited statistical power, most studies identify only small numbers of candidate genes that pass the conventional significance thresholds (e.g. P ≤ 5 × 10-8). This limitation can be partly overcome by increasing the sample size, but this comes at a higher cost. Alternatively, weak association signals can be boosted by incorporating independent data. Previously, we demonstrated the feasibility of boosting GWAS disease associations using gene networks. Here, we present a web server, GWAB (www.inetbio.org/gwab), for the network-based boosting of human GWAS data. Using GWAS summary statistics (P-values) for SNPs along with reference genes for a disease of interest, GWAB reprioritizes candidate disease genes by integrating the GWAS and network data. We found that GWAB could more effectively retrieve disease-associated reference genes than GWAS could alone. As an example, we describe GWAB-boosted candidate genes for coronary artery disease and supporting data in the literature. These results highlight the inherent value in sub-threshold GWAS associations, which are often not publicly released. GWAB offers a feasible general approach to boost such associations for human disease genetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / pathology
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Data Interpretation, Statistical
  • Gene Expression Regulation
  • Gene Regulatory Networks*
  • Genes, Essential
  • Genome, Human*
  • Genome-Wide Association Study
  • Humans
  • Internet
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Polymorphism, Single Nucleotide*
  • Sample Size
  • Software*
  • Soluble Guanylyl Cyclase / genetics
  • Soluble Guanylyl Cyclase / metabolism

Substances

  • Amyloid beta-Protein Precursor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • GUCY1B1 protein, human
  • Pecam1 protein, mouse
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Soluble Guanylyl Cyclase