title: Pharmacometabolomics informs Pharmacogenomics.
abstract: BACKGROUND
  The initial decades of the 21stcentury have witnessed striking technical advances that have made it possible to detect, identify and quantitatively measure large numbers of plasma or tissue metabolites. In parallel, similar advances have taken place in our ability to sequence DNA and RNA. Those advances have moved us beyond studies of single metabolites and single genetic polymorphisms to the study of hundreds or thousands of metabolites and millions of genomic variants in a single cell or subject. It is now possible to merge and integrate large data sets generated by the use of different "-omics" techniques to increase our understanding of the molecular basis for variation in disease risk and/or drug response phenotypes.
  
  
  OBJECTIVE
  This "Brief Review" will outline some of the challenges and opportunities associated with studies in which metabolomic data have been merged with genomics in an attempt to gain novel insight into mechanisms associated with variation in drug response phenotypes, with an emphasis on the application of a pharmacometabolomics-informed pharmacogenomic research strategy and with selected examples of the application of that strategy.
  
  
  METHODS
  Studies that used pharmacometabolomics to inform and guide pharmacogenomics were reviewed. Clinical studies that were used as the basis for pharmacometabolomics-informed pharmacogenomic studies, published in five independent manuscripts, are described briefly.
  
  
  RESULTS
  Within these five manuscripts, both pharmacokinetic and pharmacodynamic metabolomics approaches were used. Candidate gene and genome-wide approaches that were used in concert with these metabolomic data identified novel metabolite-gene relationships that were associated with drug response phenotypes in these pharmacometabolomics-informed pharmacogenomics studies.
  
  
  CONCLUSIONS
  This "Brief Review" outlines the emerging discipline of pharmacometabolomics-informed pharmacogenomics in which metabolic profiles are associated with both clinical phenotypes and genetic variants to identify novel genetic variants associated with drug response phenotypes based on metabolic profiles.
authors: Department of Molecular Pharmacology and Experimental Therapeutics, 200 First Street SW, Mayo Clinic, Rochester, MN 55905.
authors: Drew
authors: D
authors: Neavin
authors: Department of Psychiatry and Behavioral Medicine, Duke Institute for Brain Sciences, 3552, Blue Zone, Duke South, Durham, NC 27710.
authors: Rima
authors: R
authors: Kaddurah-Daouk
authors: Department of Molecular Pharmacology and Experimental Therapeutics, 200 First Street SW, Mayo Clinic, Rochester, MN 55905.
authors: Richard
authors: R
authors: Weinshilboum
keywords: Pharmacometabolomics; metabolomics; pharmacogenomics