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Pharmacogenomics

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Abstract

Pharmacogenomics is a rapidly growing field dedicated to identifying genetic markers that will allow practitioners to identify safe and effective therapy that is tailored to the individual patient. As a result, pharmacogenomic testing has the potential to optimize drug therapy for a variety of disease states. The landmark Sequenced Treatment Alternatives to Relieve Depression trial, commonly known as the STAR*D trial, showed that only a disappointing 30 % of patients experience remission from depression symptoms with their initial trial of antidepressant therapy. Furthermore, other studies have shown that 70 % of patients not remitting after their first medication trial may endure symptoms for months before experiencing relief secondary to drug therapy. In the future it is hoped that advancing pharmacogenomics research will help identify the safest and most effective medication for each patient—not only for the treatment of depression but for other disease states as well. Currently pharmacogenomic testing is not widely implemented; however, this is likely to change as clinicians become increasingly familiar with this field. This chapter will familiarize clinicians with the field of pharmacogenomics by (1) building a simple understanding of how genetic variability can alter drug response, (2) discussing current approaches in pharmacogenomics research, (3) describing helpful resources for practitioners, (4) providing an overview of the clinical application of pharmacogenomics and the associated issue of reimbursement, and (5) reviewing opinions on the future of pharmacogenomics in the clinical setting.

Kristen M. Wiese and Stephanie A. Flowers contributed equally to this work.

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References

  1. Rush AJ, Trivedi MH, Wisniewski SR et al (2006) Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 163:1905–1917

    Article  PubMed  Google Scholar 

  2. Trivedi MH, Rush AJ, Wisniewski SR et al (2006) Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 163:28–40

    Article  PubMed  Google Scholar 

  3. Gelenberg AJ, Freeman MP, Markowitz JC et al (2010) Practice guideline for the treatment of patients with major depressive disorder. Retrieved from: http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf

  4. Genetics Home Reference, U.S. National Library of Medicine (2015) What is the International HapMap Project? (2014). Retrieved from: http://ghr.nlm.nih.gov/handbook/genomicresearch/hapmap

  5. Redon R, Ishikawa S, Fitch KR et al (2006) Global variation in copy number in the human genome. Nature 444:444–454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ouahchi K, Lindeman N, Lee C (2006) Copy number variants and pharmacogenomics. Pharmacogenomics 7:25–29

    Article  CAS  PubMed  Google Scholar 

  7. Clayton AH, Montejo AL (2006) Major depressive disorder, antidepressants, and sexual dysfunction. J Clin Psychiatry 67 Suppl 6:33–37

    PubMed  Google Scholar 

  8. Higgins A, Nash M, Lynch AM (2010) Antidepressant-associated sexual dysfunction: impact, effects, and treatment. Drug Healthc Patient Saf 2:141–150

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kennedy SH, Rizvi S (2009) Sexual dysfunction, depression, and the impact of antidepressants. J Clin Psychopharmacol 29:157–164

    Article  CAS  PubMed  Google Scholar 

  10. Barr CS, Newman TK, Schwandt M et al (2004) Sexual dichotomy of an interaction between early adversity and the serotonin transporter gene promoter variant in rhesus macaques. Proc Natl Acad Sci U S A 101:12358–12363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Strohmaier J, Wüst S, Uher R et al (2011) Sexual dysfunction during treatment with serotonergic and noradrenergic antidepressants: clinical description and the role of the 5-HTTLPR. World J Biol Psychiatry 12:528–538

    Article  PubMed  PubMed Central  Google Scholar 

  12. Lesch KP, Bengel D, Heils A et al (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527–1531

    Article  CAS  PubMed  Google Scholar 

  13. Gillihan SJ, Rao H, Wang J et al (2010) Serotonin transporter genotype modulates amygdala activity during mood regulation. Soc Cogn Affect Neurosci 5:1–10

    Article  PubMed  PubMed Central  Google Scholar 

  14. Zanardi R, Serretti A, Rossini D et al (2001) Factors affecting fluvoxamine antidepressant activity: influence of pindolol and 5-HTTLPR in delusional and nondelusional depression. Biol Psychiatry 50:323–330

    Article  CAS  PubMed  Google Scholar 

  15. Peters EJ, Slager SL, McGrath PJ, Knowles JA, Hamilton SP (2004) Investigation of serotonin-related genes in antidepressant response. Mol Psychiatry 9:879–889

    Article  CAS  PubMed  Google Scholar 

  16. Bishop JR, Ellingrod VL, Akroush M et al (2009) The association of serotonin transporter genotypes and selective serotonin reuptake inhibitor (SSRI)-associated sexual side effects: possible relationship to oral contraceptives. Hum Psychopharmacol 24:207–215

    Article  CAS  PubMed  Google Scholar 

  17. Daly AK (2010) Genome-wide association studies in pharmacogenomics. Nat Rev Genet 11:241–246

    Article  CAS  PubMed  Google Scholar 

  18. Yang TH, Kon M, DeLisi C (2013) Genome-wide association studies. Methods Mol Biol 939:233–251

    Article  CAS  PubMed  Google Scholar 

  19. Hayes B (2013) Overview of statistical methods for genome-wide association studies (GWAS). Methods Mol Biol 1019:149–169

    Article  PubMed  Google Scholar 

  20. No authors listed (2010) On beyond GWAS. Nat Genet 42:551

    Google Scholar 

  21. Edwards SL, Beesley J, French JD et al (2013) Beyond GWASs: illuminating the dark road from association to function. Am J Hum Genet 93:779–797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Laje G, Perlis RH, Rush AJ et al (2009) Pharmacogenetics studies in STAR*D: strengths, limitations, and results. Psychiatr Serv 60:1446–1457

    Article  PubMed  PubMed Central  Google Scholar 

  23. McMahon FJ, Buervenich S, Charney D et al (2006) Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment. Am J Hum Genet 78:804–814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Paddock S, Laje G, Charney D et al (2007) Association of GRIK4 with outcome of antidepressant treatment in the STAR*D cohort. Am J Psychiatry 164:1181–1188

    Article  PubMed  Google Scholar 

  25. Lander ES (2011) Initial impact of the sequencing of the human genome. Nature 470:187–197

    Article  CAS  PubMed  Google Scholar 

  26. Bao R, Huang L, Andrade J et al (2014) Review of current methods, applications, and data management for the bioinformatics analysis of whole exome sequencing. Cancer Inform 13:67–82

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Rabbani B, Teki M, Mahdieh N (2014) The promise of whole-exome sequencing in medical genetics. J Hum Genet 59:5–15

    Article  CAS  PubMed  Google Scholar 

  28. Wong ML, Dong C, Flores DL et al (2014) Clinical outcomes and genome-wide association for a brain methylation site in an antidepressant pharmacogenetics study in Mexican Americans. Am J Psychiatry 171:1297–1309

    Article  PubMed  Google Scholar 

  29. Cirulli ET, Goldstein DB (2010) Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet 11:415–425

    Article  CAS  PubMed  Google Scholar 

  30. Yu Y, Wu B, Wu J et al (2012) Exome and whole-genome sequencing as clinical tests: a transformative practice in molecular diagnostics. Clin Chem 58:1507–1509

    Article  CAS  PubMed  Google Scholar 

  31. Ng PC, Kirkness EF (2010) Whole genome sequencing. Methods Mol Biol 628:215–226

    Article  CAS  PubMed  Google Scholar 

  32. Mizzi C, Peters B, Mitropoulou C et al (2014) Personalized pharmacogenomics profiling using whole-genome sequencing. Pharmacogenomics 15:1223–1234

    Article  CAS  PubMed  Google Scholar 

  33. Sebat J, Lakshmi B, Troge J et al (2004) Large-scale copy number polymorphism in the human genome. Science 305:525–528

    Article  CAS  PubMed  Google Scholar 

  34. Estivill X, Armengol L (2007) Copy number variants and common disorders: filling the gaps and exploring complexity in genome-wide association studies. PLoS Genet 3:1787–1799

    Article  CAS  PubMed  Google Scholar 

  35. Hooli BV, Kovacs-Vajna ZM, Mullin K et al (2014) Rare autosomal copy number variations in early-onset familial Alzheimer’s disease. Mol Psychiatry 19:676–681

    Article  CAS  PubMed  Google Scholar 

  36. Merikangas AK, Segurado R, Cormican P et al (2014) The phenotypic manifestations of rare CNVs in schizophrenia. Schizophr Res 158:255–260

    Article  PubMed  Google Scholar 

  37. Coe BP, Witherspoon K, Rosenfeld JA et al (2014) Refining analyses of copy number variation identifies specific genes associated with developmental delay. Nat Genet 46:1063–1071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zhou SF, Liu JP, Lai XS (2009) Substrate specificity, inhibitors and regulation of human cytochrome P450 2D6 and implications in drug development. Curr Med Chem 16:2661–2805

    Article  CAS  PubMed  Google Scholar 

  39. Hosono N, Kato M, Kiyotani K et al (2009) CYP2D6 genotyping for functional-gene dosage analysis by allele copy number detection. Clin Chem 55:1546–1554

    Article  CAS  PubMed  Google Scholar 

  40. National Institutes of Health (2008) DailyMed – CARBAMAZEPINE- carbamazepine tablet CARBAMAZEPINE- carbamazepine tablet, chewable. Retrieved from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c13bc0b8-7900-4ef4-98ed-e1315a08d95d

  41. Ferrell PB, McLeod HL (2008) Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics 9:1543–1546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hung SI, Chung WH, Jee SH et al (2006) Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics 16:297–306

    Article  CAS  PubMed  Google Scholar 

  43. U.S. Food and Drug Administration (2013) Postmarket drug safety information for patients and providers – information for healthcare professionals: dangerous or even fatal skin reactions – carbamazepine (marketed as Carbatrol, Equetro, Tegretol, and generics). Retrieved from: http://www.fda.gov/Drugs/DrugSafety/Postmarket.DrugSafetyInformationforPatientsandProviders/ucm124718.htm

  44. PharmGKB. DPWG: Dutch Pharmacogenetics Working Group. Retrieved from: https://www.pharmgkb.org/page/dpwg

  45. PharmGKB. CPIC: clinical pharmacogenetics implementation consortium. Retrieved from: https://www.pharmgkb.org/page/cpic

  46. Hicks JK, Swen JJ, Thorn CF et al (2013) Clinical pharmacogenetics implementation consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin Pharmacol Ther 93:402–408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. National Human Genome Research Institute (2015) Regulation of genetic tests. Retrieved from: http://www.genome.gov/10002335

  48. Centers for Medicare & Medicaid Services (2014) Clinical laboratory improvements amendments (CLIA). Retrieved from: http://www.cms.gov/Regulations-and-Guidance/Legislation/CLIA/index.html?redirect=/clia/

  49. Genetics Home Reference, U.S. National Library of Medicine (2014) How can consumers be sure a genetic test is valid and useful? Retrieved from: http://ghr.nlm.nih.gov/handbook/testing/validtest

  50. Robert J, Milligan RJ (2008) Coverage and reimbursement for pharmacogenomic testing. Jurimetrics J 48:137–165

    Google Scholar 

  51. Priority Health (2010) Pharmacogenomic testing. Retrieved from: https://www.priorityhealth.com/provider/manual/auths/~/media/documents/medical-policies/91570.pdf

  52. Crettol S, de Leo J, Hiemke C, Eap CB (2014) Pharmacogenomics in psychiatry: from therapeutic drug monitoring to genomic medicine. Clin Pharmacol Ther 95:254–257

    Article  CAS  PubMed  Google Scholar 

  53. Perlis RH, Patrick A, Smoller JW et al (2009) When is pharmacogenetic testing for antidepressant response ready for the clinic? A cost-effectiveness analysis based on data from the STAR*D study. Neuropsychopharmacology 34:2227–2236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Santa Clara University (2008) Pharmacogenomics, ethics, and public policy. Retrieved from: http://www.scu.edu/ethics/practicing/focusareas/medical/pharmacogenomics.html

  55. Genetics Home Reference, U.S. National Library of Medicine (2015) The genetic information nondiscrimination act (GINA). (2014). Retrieved from: http://ghr.nlm.nih.gov/spotlight=thegeneticinformationnondiscriminationactgina

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Correspondence to Vicki L. Ellingrod PharmD, FCCP .

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Wiese, K.M., Flowers, S.A., Ellingrod, V.L. (2016). Pharmacogenomics. In: Jann, M., Penzak, S., Cohen, L. (eds) Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological Agents. Adis, Cham. https://doi.org/10.1007/978-3-319-27883-4_6

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  • DOI: https://doi.org/10.1007/978-3-319-27883-4_6

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