Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets

Sci Rep. 2018 Feb 21;8(1):3434. doi: 10.1038/s41598-018-20721-6.


Genome-wide association studies (GWAS) have identified over two hundred chromosomal loci that modulate risk of coronary artery disease (CAD). The genes affected by variants at these loci are largely unknown and an untapped resource to improve our understanding of CAD pathophysiology and identify potential therapeutic targets. Here, we prioritized 68 genes as the most likely causal genes at genome-wide significant loci identified by GWAS of CAD and examined their regulatory roles in 286 metabolic and vascular tissue gene-protein sub-networks ("modules"). The modules and genes within were scored for CAD druggability potential. The scoring enriched for targets of cardiometabolic drugs currently in clinical use and in-depth analysis of the top-scoring modules validated established and revealed novel target tissues, biological processes, and druggable targets. This study provides an unprecedented resource of tissue-defined gene-protein interactions directly affected by genetic variance in CAD risk loci.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coronary Artery Disease / drug therapy
  • Coronary Artery Disease / genetics*
  • Drug Discovery
  • Gene Regulatory Networks* / drug effects
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Linkage Disequilibrium
  • Molecular Targeted Therapy
  • Polymorphism, Single Nucleotide / drug effects
  • Quantitative Trait Loci / drug effects