Characterization of statin dose response in electronic medical records

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, Robert Davis, R. L. Berg, P. L. Peissig, C. A. McCarty, R. A. Wilke, J. C. Denny

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 (ED 50) and efficacy (E max) 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 E max for both. For atorvastatin, E max 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 ED 50. 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.

Original languageEnglish (US)
Pages (from-to)331-338
Number of pages8
JournalClinical Pharmacology and Therapeutics
Volume95
Issue number3
DOIs
StatePublished - Mar 1 2014
Externally publishedYes

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Electronic Health Records
Simvastatin
Alleles
Pharmaceutical Preparations
Atorvastatin Calcium

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Wei, W. Q., Feng, Q., Jiang, L., Waitara, M. S., Iwuchukwu, O. F., Roden, D. M., ... Denny, J. C. (2014). Characterization of statin dose response in electronic medical records. Clinical Pharmacology and Therapeutics, 95(3), 331-338. https://doi.org/10.1038/clpt.2013.202

Characterization of statin dose response in electronic medical records. / Wei, W. Q.; Feng, Q.; Jiang, L.; Waitara, M. S.; Iwuchukwu, O. F.; Roden, D. M.; Jiang, M.; Xu, H.; Krauss, R. M.; Rotter, J. I.; Nickerson, D. A.; Davis, Robert; Berg, R. L.; Peissig, P. L.; McCarty, C. A.; Wilke, R. A.; Denny, J. C.

In: Clinical Pharmacology and Therapeutics, Vol. 95, No. 3, 01.03.2014, p. 331-338.

Research output: Contribution to journalArticle

Wei, WQ, Feng, Q, Jiang, L, Waitara, MS, Iwuchukwu, OF, Roden, DM, Jiang, M, Xu, H, Krauss, RM, Rotter, JI, Nickerson, DA, Davis, R, Berg, RL, Peissig, PL, McCarty, CA, Wilke, RA & Denny, JC 2014, 'Characterization of statin dose response in electronic medical records', Clinical Pharmacology and Therapeutics, vol. 95, no. 3, pp. 331-338. https://doi.org/10.1038/clpt.2013.202
Wei WQ, Feng Q, Jiang L, Waitara MS, Iwuchukwu OF, Roden DM et al. Characterization of statin dose response in electronic medical records. Clinical Pharmacology and Therapeutics. 2014 Mar 1;95(3):331-338. https://doi.org/10.1038/clpt.2013.202
Wei, W. Q. ; Feng, Q. ; Jiang, L. ; Waitara, M. S. ; Iwuchukwu, O. F. ; Roden, D. M. ; Jiang, M. ; Xu, H. ; Krauss, R. M. ; Rotter, J. I. ; Nickerson, D. A. ; Davis, Robert ; Berg, R. L. ; Peissig, P. L. ; McCarty, C. A. ; Wilke, R. A. ; Denny, J. C. / Characterization of statin dose response in electronic medical records. In: Clinical Pharmacology and Therapeutics. 2014 ; Vol. 95, No. 3. pp. 331-338.
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