The pharmacoepigenomics informatics pipeline defines a pathway of novel and known warfarin pharmacogenomics variants

Pharmacogenomics. 2018 Apr;19(5):413-434. doi: 10.2217/pgs-2017-0186. Epub 2018 Feb 5.

Abstract

Aim: 'Pharmacoepigenomics' methods informed by omics datasets and pre-existing knowledge have yielded discoveries in neuropsychiatric pharmacogenomics. Now we evaluate the generality of these methods by discovering an extended warfarin pharmacogenomics pathway.

Materials & methods: We developed the pharmacoepigenomics informatics pipeline, a scalable multi-omics variant screening pipeline for pharmacogenomics, and conducted an experiment in the genomics of warfarin.

Results: We discovered known and novel pharmacogenomics variants and genes, both coding and regulatory, for warfarin response, including adverse events. Such genes and variants cluster in a warfarin response pathway consolidating known and novel warfarin response variants and genes.

Conclusion: These results can inform a new warfarin test. The pharmacoepigenomics informatics pipeline may be able to discover new pharmacogenomics markers in other drug-disease systems.

Keywords: GWAS; anticoagulation PGx; cardiovascular PGx.

Publication types

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

MeSH terms

  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Blood Coagulation Disorders / drug therapy
  • Blood Coagulation Disorders / genetics
  • Computational Biology*
  • Genetic Variation / genetics
  • Genome-Wide Association Study
  • Humans
  • Lithium Compounds / therapeutic use
  • Pharmacogenetics*
  • Polymorphism, Single Nucleotide
  • Warfarin / adverse effects
  • Warfarin / therapeutic use*

Substances

  • Anticoagulants
  • Lithium Compounds
  • Warfarin