Leveraging human genetics to guide drug target discovery

Trends Cardiovasc Med. 2017 Jul;27(5):352-359. doi: 10.1016/j.tcm.2016.08.008. Epub 2016 Aug 26.


Identifying appropriate molecular targets is a critical step in drug development. Despite many advantages, the traditional tools of observational epidemiology and cellular or animal models of disease can be misleading in identifying causal pathways likely to lead to successful therapeutics. Here, we review some favorable aspects of human genetics studies that have the potential to accelerate drug target discovery. These include using genetic studies to identify pathways relevant to human disease, leveraging human genetics to discern causal relationships between biomarkers and disease, and studying genetic variation in humans to predict the potential efficacy and safety of inhibitory compounds aimed at molecular targets. We present some examples taken from studies of plasma lipids and coronary artery disease to highlight how human genetics can accelerate therapeutics development.

Keywords: Cardiovascular disease; Human genetics.

Publication types

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

MeSH terms

  • Animals
  • Cardiovascular Agents / adverse effects
  • Cardiovascular Agents / therapeutic use*
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Drug Discovery / methods*
  • Genetic Predisposition to Disease
  • Genomics*
  • Humans
  • Molecular Targeted Therapy
  • Pharmacogenetics
  • Phenotype
  • Risk Factors
  • Signal Transduction / drug effects


  • Cardiovascular Agents