Capitalizing on Insights from Human Genetics to Identify Novel Therapeutic Targets for Coronary Artery Disease

Annu Rev Med. 2019 Jan 27:70:19-32. doi: 10.1146/annurev-med-041717-085853. Epub 2018 Oct 24.

Abstract

Coronary artery disease (CAD) is a major cause of morbidity and mortality. Unfortunately, despite decades of research focused on disease pathogenesis, we still lack a sufficient pharmacopeia for preventing CAD. The failure of many novel cardiovascular drugs to improve clinical outcomes reflects the major substantial challenge of drug development: identifying causal mechanisms that can be therapeutically manipulated to lower disease risk. Identifying genetic variants that are associated with risk of CAD has emerged as a clear path toward improving our understanding of the underlying mechanisms that lead to disease and to the development of new therapies. Here, we review the potential utility and limitations of using human genetics to guide the identification of therapeutic targets for CAD.

Keywords: coronary artery disease; drug development; genetics of complex disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cardiovascular Agents / administration & dosage
  • Cardiovascular Agents / pharmacology*
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / physiopathology
  • Drug Approval
  • Drug Development
  • Female
  • Genetic Predisposition to Disease / epidemiology*
  • Genome-Wide Association Study*
  • Human Genetics
  • Humans
  • Male
  • Molecular Targeted Therapy / methods*

Substances

  • Cardiovascular Agents