Journal Mobile Options
Table of Contents
Vol. 12, No. 3, 2009
Issue release date: February 2009
Public Health Genomics 2009;12:142–148

Trends in Pharmacogenomic Epidemiology: 2001–2007

Guessous I. · Gwinn M. · Yu W. · Yeh J. · Clyne M. · Khoury M.J.
aEmory University, Rollins School of Public Health Department of Epidemiology, and bThe National Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, Ga., USA

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background: Pharmacogenomic epidemiology (PGxE) assesses the range of responses to pharmacologic agents in relation to genetic variation in population groups. We analyzed publication trends to describe the emerging field of PGxE. Methods: We analyzed PGxE literature published from 2001 to 2007 by using the HuGE Navigator, a curated database of abstracts on human genome epidemiology extracted from PubMed. We summarized trends by gene and study design and, for the 4 most cited genes, by associated health outcomes and drugs. Results: In all, 1,855 PGxE articles were indexed from 2001 through 2007, with annual publications increasing more than 15-fold during this period. Observational studies outnumbered clinical trials by a ratio of 10 to 1 (1,660 vs. 178). Just 4 genes together accounted for nearly one-fifth of all publications: ABCB1, CYP2C9, CYP2C19, and CYP2D6. For these 4 genes, the most frequently cited therapeutic category was antineoplastic agent, followed by anticoagulant, antiulcer, and antidepressant. Warfarin was the single most frequently cited drug. Conclusions: The field of PGxE is growing rapidly, encompassing a large spectrum of diseases and drugs important in clinical practice. Systematic tracking and synthesis of the published literature in PGxE can help identify promising applications and guide translation research.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Kalow W: Historical aspect of pharmacogenetics; in Kalow W, Meyer UA, Tyndale RF (eds): Pharmacogenomics, 2nd ed. Abingdon, Taylor & Francis, 2005, pp 1.
  2. Goldstein DB, Tate SK, Sisodiya SM: Pharmacogenetics goes genomic. Nat Rev Genet 2003;4:937–947.
  3. Collins FS, McKusick VA: Implications of the Human Genome Project for medical science. JAMA 2001;285:540–544.
  4. Roses AD: Pharmacogenetics and future drug development and delivery. Lancet 2000;355:1358–1361.
  5. Evans WE, Relling MV: Moving towards individualized medicine with pharmacogenomics. Nature 2004;429:464–468.
  6. Haga SB, Burke W: Using pharmacogenetics to improve drug safety and efficacy. JAMA 2004;291:2869–2871.
  7. O’Brien TG: Ornithine decarboxylase polymorphism modification of response to aspirin treatment for colorectal adenoma prevention. J Natl Cancer Inst 2006;98:1494–1500.
  8. Laje G, Paddock S, Manji H, Rush AJ, Wilson AF, Charney D, McMahon FJ: Genetic markers of suicidal ideation emerging during citalopram treatment of major depression. Am J Psychiatry 2007;164:1530–1538.
  9. Kuivenhoven JA, Jukema JW, Zwinderman AH, de Knijff P, McPherson R, Bruschke AV, Lie KI, Kastelein JJ: The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. The Regression Growth Evaluation Statin Study Group. N Engl J Med 1998;338:86–93.
  10. Aithal GP, Day CP, Kesteven PJ, Daly AK: Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 1999;353:717–719.
  11. Tan S, Hall IP, Dewar J, Dow E, Lipworth B: Association between beta 2-adrenoceptor polymorphism and susceptibility to bronchodilator desensitisation in moderately severe stable asthmatics. Lancet 1997;350:995–999.
  12. Gerloff T, Schaefer M, Johne A, Oselin K, Meisel C, Cascorbi I, Roots I: MDR1 genotypes do not influence the absorption of a single oral dose of 1 mg digoxin in healthy white males. Br J Clin Pharmacol 2002;54:610–616.
  13. Roberts RL, Joyce PR, Mulder RT, Begg EJ, Kennedy MA: A common P-glycoprotein polymorphism is associated with nortriptyline-induced postural hypotension in patients treated for major depression. Pharmacogenomics J 2002;2:191–196.
  14. De Luca V, Mundo E, Trakalo J, Wong GW, Kennedy JL: Investigation of polymorphism in the MDR1 gene and antidepressant-induced mania. Pharmacogenomics J 2003;3:297–299.
  15. National Library of Medicine. MESH database, (accessed February 22, 2008).
  16. International Society of Pharmacoepidemiology, (accessed February 22, 2008).
  17. Lapane K, Weinstock MA: The power and limitations of pharmacogenetic epidemiology. J Invest Dermatol 2007;127:1851–1852.
  18. Little J, Sharp L, Khoury MJ, Bradley L, Gwinn M: The epidemiologic approach to pharmacogenomics. Am J Pharmacogenomics 2005;5:1–20.
  19. Jones JK: Pharmacogenetics and pharmacoepidemiology. Pharmacoepidemiol Drug Saf 2001;10:457–461.
  20. Maitland-van der Zee AH, de Boer A, Leufkens HG: The interface between pharmacoepidemiology and pharmacogenetics. Eur J Pharmacol 2000;410:121–130.
  21. University of Pennsylvania’s Clinical Pharmacogenomic Epidemiology (CPE) initiative, (accessed February 22, 2008).
  22. Ray WA: Population-based studies of adverse drug effects. N Engl J Med 2003;349:1592–1594.
  23. Rothstein MA: Pharmacogenomics. Social, Ethical, and Clinical Dimensions. San Francisco, Wiley, 2003.
  24. Yu W, Gwinn M, Clyne M, Yesupriya A, Khoury MJ: A navigator for human genome epidemiology. Nat Genet 2008;40:124–125.
  25. Lin BK, Clyne M, Walsh M, Gomez O, Yu W, Gwinn M, Khoury MJ: Tracking the epidemiology of human genes in the literature: the HuGE Published Literature database. Am J Epidemiol 2006;164:1–4.
  26. Yu W, Clyne M, Dolan SM, Yesupriya A, Wulf A, Liu T, Khoury MJ, Gwinn M: GAPscreener: an automatic tool for screening human genetic association literature in PubMed using the support vector machine technique. BMC Bioinformatics 2008;9:205.
  27. The NLM Unified Medical Language System (UMLS), (accessed February 22, 2008).
  28. Swen JJ, Huizinga TW, Gelderblom H, de Vries EG, Assendelft WJ, Kirchheiner J, Guchelaar HJ: Translating pharmacogenomics: challenges on the road to the clinic. PLoS Med 2007;4:e209.
  29. Leschziner GD, Andrew T, Pirmohamed M, Johnson MR: ABCB1 genotype and PGP expression, function and therapeutic drug response: a critical review and recommendations for future research. Pharmacogenomics J 2007;7:154–179.
  30. Essioux L, Destenaves B, Jais P, Thomas F: Associations studies in pharmacogenomics; in Licinio J, Wong MA (eds): Pharmacogenomics. The Search for Individualized Therapies, 1st ed. San Francisco, Wiley, 2002, pp 58–60.
  31. Flockhart DA, O’Kane D, Williams MS, Watson MS, Flockhart DA, Gage B, Gandolfi R, King R, Lyon E, Nussbaum R, O’Kane D, Schulman K, Veenstra D, Williams MS, Watson MS; ACMG Working Group on Pharmacogenetic Testing of CYP2C9, VKORC1 Alleles for Warfarin Use: Pharmacogenetic testing of CYP2C9 and VKORC1 alleles for warfarin. Genet Med 2008;10:139–150.
  32. Schwarz UI, Ritchie MD, Bradford Y, Li C, Dudek SM, Frye-Anderson A, Kim RB, Roden DM, Stein CM: Genetic determinants of response to warfarin during initial anticoagulation. New Engl J Med 2008;358:999–1008.
  33. American College of Medical Genetics responds to new FDA labeling decision for warfarin: ACMG releases comprehensive review of genetic testing and warfarin dosing, (accessed March 17, 2008).
  34. Personalized health care report 2008: warfarin and genetic testing, (accessed March 28, 2008).
  35. Meyer UA: Pharmacogenetics and adverse drug reactions. Lancet 2000;356:1667–1671.
  36. Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W: Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA 2001;286:2270–2279.
  37. Gwinn M, Khoury MJ: Epidemiologic approach to genetic tests: population-based data for preventive medicine; in Khoury MJ, Little J, Burke W (eds): Human Genome Epidemiology. A Scientific Foundation for Using Genetic Information to Improve Health and Prevent Disease. Oxford, Oxford University Press, 2004, pp 195–206.
  38. Meyer UA: Pharmacogenetics – five decades of therapeutic lessons from genetic diversity. Nat Rev Genet 2004;5:669–676.
  39. Rubin DL, Carrillo M, Woon M, Conroy J, Klein TE, Altman RB: A resource to acquire and summarize pharmacogenetics knowledge in the literature. Medinfo 2004;11:793–797.
  40. Colhoun HM, McKeigue PM, Davey Smith G: Problems of reporting genetic associations with complex outcomes. Lancet 2003;361:865–872.
  41. Cardon LR, Bell JI: Association study designs for complex diseases. Nat Rev Genet 2001;2:91–99.
  42. Gorroochurn P, Hodge SE, Heiman GA, Durner M, Greenberg DA: Non-replication of association studies: ‘pseudo-failures’ to replicate? Genet Med 2007;9:325–331.
  43. Moonesinghe R, Khoury MJ, Janssens AC: Most published research findings are false – but a little replication goes a long way. PLoS Med 2007;4:e28.
  44. Williams JA, Johnson K, Paulauskis J, Cook J: So many studies, too few subjects: establishing functional relevance of genetic polymorphisms on pharmacokinetics. J Clin Pharmacol 2006;46:258–264.
  45. Lesko LJ, Woodcock J: Translation of pharmacogenomics and pharmacogenetics: a regulatory perspective. Nat Rev Drug Discov 2004;3:763–769.
  46. Kirchheiner J, Fuhr U, Brockmöller J: Pharmacogenetics-based therapeutic recommendations – ready for clinical practice? Nat Rev Drug Discov 2005;4:639–647.
  47. Maitland-van der Zee AH, de Boer A, Leufkens HG: The interface between pharmacoepidemiology and pharmacogenetics. Eur J Pharmacol 200027;410:121–130.

    External Resources

  48. Long RM: Planning for a national effort to enable and accelerate discoveries in pharmacogenetics: the NIH Pharmacogenetics Research Network. Clin Pharmacol Ther 2007;81:450–454.
  49. Weinshilboum R, Wang L: Pharmacogenomics: bench to bedside. Nat Rev Drug Discov 2004;3:739–748.
  50. Burke W, Atkins D, Gwinn M, Guttmacher A, Haddow J, Lau J, Palomaki G, Press N, Richards CS, Wideroff L, Wiesner GL: Genetic test evaluation: information needs of clinicians, policy makers, and the public. Am J Epidemiol 2002;15:311–318.

    External Resources

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50