The support of human genetic evidence for approved drug indications

Nat Genet. 2015 Aug;47(8):856-60. doi: 10.1038/ng.3314. Epub 2015 Jun 29.


Over a quarter of drugs that enter clinical development fail because they are ineffective. Growing insight into genes that influence human disease may affect how drug targets and indications are selected. However, there is little guidance about how much weight should be given to genetic evidence in making these key decisions. To answer this question, we investigated how well the current archive of genetic evidence predicts drug mechanisms. We found that, among well-studied indications, the proportion of drug mechanisms with direct genetic support increases significantly across the drug development pipeline, from 2.0% at the preclinical stage to 8.2% among mechanisms for approved drugs, and varies dramatically among disease areas. We estimate that selecting genetically supported targets could double the success rate in clinical development. Therefore, using the growing wealth of human genetic data to select the best targets and indications should have a measurable impact on the successful development of new drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Mapping
  • Databases, Genetic / statistics & numerical data
  • Drug Approval / statistics & numerical data*
  • Genetic Association Studies / statistics & numerical data
  • Genetic Predisposition to Disease / genetics*
  • Genetics, Medical / methods
  • Genetics, Medical / statistics & numerical data
  • Genome-Wide Association Study / statistics & numerical data*
  • Humans
  • Linkage Disequilibrium
  • Medical Subject Headings / statistics & numerical data
  • Molecular Targeted Therapy / statistics & numerical data
  • Polymorphism, Single Nucleotide*