Predicting warfarin dosage in European-Americans and African-Americans using DNA samples linked to an electronic health record.

Pharmacogenomics
Andrea H RamirezJoshua C Denny

Abstract

Warfarin pharmacogenomic algorithms reduce dosing error, but perform poorly in non-European-Americans. Electronic health record (EHR) systems linked to biobanks may allow for pharmacogenomic analysis, but they have not yet been used for this purpose. We used BioVU, the Vanderbilt EHR-linked DNA repository, to identify European-Americans (n = 1022) and African-Americans (n = 145) on stable warfarin therapy and evaluated the effect of 15 pharmacogenetic variants on stable warfarin dose. Associations between variants in VKORC1, CYP2C9 and CYP4F2 with weekly dose were observed in European-Americans as well as additional variants in CYP2C9 and CALU in African-Americans. Compared with traditional 5 mg/day dosing, implementing the US FDA recommendations or the International Warfarin Pharmacogenomics Consortium (IWPC) algorithm reduced error in weekly dose in European-Americans (13.5-12.4 and 9.5 mg/week, respectively) but less so in African-Americans (15.2-15.0 and 13.8 mg/week, respectively). By further incorporating associated variants specific for European-Americans and African-Americans in an expanded algorithm, dose-prediction error reduced to 9.1 mg/week (95% CI: 8.4-9.6) in European-Americans and 12.4 mg/week (95% CI: 10.0-13.2...Continue Reading

References

May 11, 2005·The Pharmacogenomics Journal·M WadeliusP Deloukas
Mar 3, 2007·Clinical Pharmacology and Therapeutics·H SchellemanS E Kimmel
Jul 11, 2007·Archives of Internal Medicine·Diane K WysowskiLynette Swartz
Sep 4, 2007·Journal of Thrombosis and Haemostasis : JTH·M J RiederA E Rettie
Nov 9, 2007·Circulation·Jeffrey L AndersonUNKNOWN Couma-Gen Investigators
Jan 10, 2008·Clinical Pharmacology and Therapeutics·M-S WenY-T Chen
Feb 19, 2008·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Monica R McClainJames E Haddow
Feb 29, 2008·Clinical Pharmacology and Therapeutics·B F GageH L McLeod
May 27, 2008·Clinical Pharmacology and Therapeutics·D M RodenD R Masys
Feb 21, 2009·The New England Journal of Medicine·UNKNOWN International Warfarin Pharmacogenetics ConsortiumJ A Johnson
Aug 12, 2009·Pharmacogenomics·Stuart A ScottRobert J Desnick
Sep 1, 2009·The New England Journal of Medicine·Stuart J ConnollyUNKNOWN RE-LY Steering Committee and Investigators
Jan 1, 2010·The New England Journal of Medicine·Donald Stuart Houston, Ryan Zarychanski
Jan 13, 2010·Journal of the American Medical Informatics Association : JAMIA·Hua XuJoshua C Denny
Jan 15, 2010·Clinical Pharmacology and Therapeutics·L H CavallariJ A Johnson
Feb 5, 2010·Journal of Thrombosis and Haemostasis : JTH·S A LubitzJ L Halperin
Mar 6, 2010·Blood·Nita A LimdiUNKNOWN International Warfarin Pharmacogenetics Consortium
Apr 7, 2010·American Journal of Human Genetics·Marylyn D RitchieDan M Roden
Apr 13, 2010·Journal of the American College of Cardiology·Robert S EpsteinJ Russell Teagarden
May 7, 2010·Clinical and Translational Science·Jill PulleyDaniel R Masys
Aug 25, 2010·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Logan DumitrescuDana C Crawford
Nov 19, 2010·Trials·Benjamin FrenchUNKNOWN COAG (Clarification of Optimal Anticoagulation through Genetics) Investigators
Jan 29, 2011·Journal of the American College of Cardiology·Brian S FinkelmanStephen E Kimmel
Mar 23, 2011·Genetics in Medicine : Official Journal of the American College of Medical Genetics·James K BurmesterMichael D Caldwell
Dec 23, 2011·Clinical Pharmacology and Therapeutics·J T DelaneyJ C Denny

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Citations

Sep 7, 2013·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Josh F PetersonJosh C Denny
Sep 21, 2013·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Casey Lynnette OverbyGeorge Hripcsak
Mar 3, 2012·Current Opinion in Cardiology·Quinn S WellsDan M Roden
Feb 14, 2013·PloS One·Raymond D HeatherlyBradley A Malin
May 10, 2013·Clinical Medicine & Research·Ingrid GlurichJames K Burmester
Jun 12, 2013·Cardiovascular Journal of Africa·Xolani W NjovaneBernd Rosenkranz
May 3, 2014·Science Translational Medicine·Erica BowtonJill M Pulley
Sep 11, 2013·The Pharmacogenomics Journal·W HernandezM A Perera
Jul 24, 2014·Journal of the American Medical Informatics Association : JAMIA·Hua XuJoshua C Denny
Nov 13, 2012·Annual Review of Pharmacology and Toxicology·Urs A MeyerMatthias Schwab
Jul 17, 2015·Journal of Human Genetics·Dan M Roden
Jan 21, 2014·Journal of Electrocardiology·Alex F ManiniDavid Vlahov
Dec 4, 2012·The Canadian Journal of Cardiology·Dan M Roden
Sep 12, 2015·Journal of Cardiovascular Pharmacology·Sameh Alzubiedi, Mohammad I Saleh
Jul 20, 2014·Journal of Biomedical Informatics·Raymond HeatherlyBradley A Malin
Feb 19, 2014·Journal of Biomedical Informatics·Ioana DanciuPaul A Harris
Aug 9, 2012·Thrombosis and Haemostasis·Daniel KurnikRonen Loebstein
Jun 9, 2012·British Journal of Clinical Pharmacology·Guilherme Suarez-Kurtz, Mariana R Botton
Oct 6, 2015·Journal of Carcinogenesis·Meghana V KashyapJamboor K Vishwanatha
May 31, 2015·Blood·Nita A LimdiT Mark Beasley
Nov 21, 2013·Clinical Pharmacology and Therapeutics·S L Van DriestD M Roden
Dec 3, 2014·Pharmacogenetics and Genomics·Katarzyna DrozdaLarisa H Cavallari
Dec 19, 2014·Pharmacogenomics·Vivian K KawaiC Michael Stein
Apr 29, 2016·Thrombosis and Haemostasis·Payman ShahabiNeda Gharani
Oct 18, 2016·Pharmacogenetics and Genomics·Otito F IwuchukwuC Michael Stein
Sep 6, 2015·Journal of the American Medical Informatics Association : JAMIA·Huan MoPaul A Harris
Nov 24, 2016·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Aisha QayyumMuhammad Ismail
Feb 10, 2018·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Miklos D Kertai, Andrew D Shaw
Nov 25, 2017·Clinical Pharmacology and Therapeutics·Joshua C DennyDan M Roden
Dec 17, 2015·Clinical Pharmacology and Therapeutics·D M Roden, J C Denny
Sep 27, 2014·Circulation Research·Karen Patterson
Oct 23, 2018·Pharmacogenomics·Aditi ShendreNita A Limdi
Mar 19, 2019·Omics : a Journal of Integrative Biology·Arinao NdadzaCollet Dandara

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Methods Mentioned

BETA
genotyping
Fluorescence

Software Mentioned

PLINK
R Foundation for Statistical Computing
R
Plato
SPECTRODESIGNER

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