title: Genomic architecture of pharmacological efficacy and adverse events.
abstract: The pharmacokinetic and pharmacodynamic disciplines address pharmacological traits, including efficacy and adverse events. Pharmacogenomics studies have identified pervasive genetic effects on treatment outcomes, resulting in the development of genetic biomarkers for optimization of drug therapy. Pharmacogenomics-based tests are already being applied in clinical decision making. However, despite substantial progress in identifying the genetic etiology of pharmacological response, current biomarker panels still largely rely on single gene tests with a large portion of the genetic effects remaining to be discovered. Future research must account for the combined effects of multiple genetic variants, incorporate pathway-based approaches, explore gene-gene interactions and nonprotein coding functional genetic variants, extend studies across ancestral populations, and prioritize laboratory characterization of molecular mechanisms. Because genetic factors can play a key role in drug response, accurate biomarker tests capturing the main genetic factors determining treatment outcomes have substantial potential for improving individual clinical care.
authors.affiliation: Department of Bioengineering & Therapeutic Sciences, Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Chhibber
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Kroetz
authors.forename: Kelan G
authors.initials: KG
authors.lastname: Tantisira
authors.forename: Michael
authors.initials: M
authors.lastname: McGeachie
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.forename: Robert
authors.initials: R
authors.lastname: Plenge
authors.forename: Eli
authors.initials: E
authors.lastname: Stahl
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sadee
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Pendergrass
mesh_terms: D004194:Disease / Q000235:genetics*; D004358:Drug Therapy; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D020412:Multifactorial Inheritance / Q000235:genetics; D010597:Pharmacogenetics
keywords: genetic architecture; genomics; heritability; linear mixed modeling; pharmacogenomics; polygenic architecture; polygenic modeling