Work

Characterization of Statin Dose Response in Electronic Medical Records

Year: 2013

Type: article

Study design: Observational Study

Abstract: Efforts to define the genetic architecture underlying variable statin response have met with limited success, possibly because previous studies were limited to effect based on a single dose. We leveraged electronic medical records (EMRs) to extract potency (ED50) and efficacy (Emax) of statin dose-response curves and tested them for association with 144 preselected variants. Two large biobanks were used to construct dose-response curves for 2,026 and 2,252 subjects on simvastatin and atorvastatin, respectively. Atorvastatin was more efficacious, was more potent, and demonstrated less interindividual variability than simvastatin. A pharmacodynamic variant emerging from randomized trials (PRDM16) was associated with Emax for both. For atorvastatin, Emax was 51.7 mg/dl in subjects homozygous for the minor allele vs. 75.0 mg/dl for those homozygous for the major allele. We also identified several loci associated with ED50. The extraction of rigorously defined traits from EMRs for pharmacogenetic studies represents a promising approach to further understand the genetic factors contributing to drug response.

Source: Clinical Pharmacology & Therapeutics

DOI: 10.1038/clpt.2013.202

Authors: W-Q Wei, Q Feng, L Jiang, M S Waitara, O F Iwuchukwu, D M Roden, M Jiang, H Xu, R M Krauss, J I Rotter, D A Nickerson, R L Davis, R L Berg, P L Peissig, C A McCarty, R A Wilke, J C Denny

Institutions: Vanderbilt University, Vanderbilt University Medical Center, The Lundquist Institute, Harbor–UCLA Medical Center, University of Washington, Kaiser Permanente, Marshfield Clinic Research Foundation, Marshfield Clinic Research Institute, Essentia Health, Sanford Medical Center

Language: English

Topic: Lipoproteins and Cardiovascular Health

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences

Awards: Pharmacogenomics of Arrhythmia Therapy, Center for Clinical and Translational Sciences (CCTS), G1781505003, National Infrastructure for Standardized and Portable EHR Phenotyping Algorithms, Pharmacogenomics and Risk of Cardiovascular Disease, UCLA Clinical and Translational Science Institute, Institutional Clinical and Translational Science Award, The Vanderbilt Institute for Clinical and Translational Research (VICTR) UL1, VESPA: Vanderbilt Electronic Systems for Pharmacogenomic Assessment, The Vanderbilt Institute for Clinical and Translational Research (VICTR), Clinical Pharmacology Training Program, Diabetes Research Center (DRC)

OpenAlex ID: W2036420216

FWCI: 4.604

Cites: 41

Cited by: 32

Related to: 10