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The Role of Genetic Testing for Parkinson’s Disease

  • Movement Disorders (T. Simuni, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To describe current practices and attitudes about genetic testing for Parkinson’s disease (PD) among neurologists, highlight the changing scene of genetic testing for PD, and provide guidance on facilitating PD genetic testing in a clinical practice.

Recent Findings

Since the 1990s, researchers have discovered several major gene variants contributing to PD etiology. A large body of literature now exists supporting the frequency of these variants in different populations and their effects on phenotype and clinical course. Recently, clinical trials have emerged with therapies targeting genetic forms of PD, specifically LRRK2 and GBA. Despite this growing knowledge, genetic testing for PD is not typically offered by neurologists including movement disorder specialists. Neurologists express concerns about the financial and practical issues of genetic testing as well as the potential impact on their patients. Researchers and specialists in the field are questioning this hesitation as clinical utility and consumer demand increase.

Summary

Consideration of genetic testing for PD is shifting, as we enter a new era of precision medicine and gain clinical knowledge about PD. Barriers to testing, as perceived by clinicians, can be overcome with education, support, and involvement of multiple stakeholders with the goal of making PD genetic testing accessible to all patients.

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References

  1. Cook Shukla L, Schulze J, Farlow J, Pankratz ND, Wojcieszek J, Foroud T. Parkinson disease overview [Internet]. Seattle: University of Washington; 2019. [cited 2019 Sep 24]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1223/

    Google Scholar 

  2. Tysnes O-B, Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm (Vienna). 2017;124(8):901–5.1.

    Article  Google Scholar 

  3. Kim CY, Alcalay RN. Genetic forms of Parkinson’s disease. Semin Neurol. 2017;37(2):135–46.

    Article  Google Scholar 

  4. Reed X, Bandrés-Ciga S, Blauwendraat C, Cookson MR. The role of monogenic genes in idiopathic Parkinson’s disease. Neurobiol Dis. 2019;124:230–9.

    Article  CAS  Google Scholar 

  5. Nalls MA, Blauwendraat C, Vallerga CL, Heilbron K, Bandres-Ciga S, Chang D, et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 2019;18(12):1091–102.

    Article  CAS  Google Scholar 

  6. Biesecker B. Genetic counseling and the central tenets of practice. Cold Spring Harb Perspect Med. 2020;10(3).

  7. Kilbride MK, Bradbury AR. Evaluating web-based direct-to-consumer genetic tests for cancer susceptibility. JCO Precis Oncol. 2020;4:161–9.

    Article  Google Scholar 

  8. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–24.

    Article  Google Scholar 

  9. Cook L, Schulze J, Kopil C, Hastings T, Naito A, Wojcieszek J, et al. Genetic testing for Parkinson disease. Neurology. 2020;11. https://doi.org/10.1212/CPJ.0000000000000831.

  10. Goldman JS, Hahn SE, Catania JW, LaRusse-Eckert S, Butson MB, Rumbaugh M, et al. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med. 2011;13(6):597–605.

    Article  Google Scholar 

  11. Nance MA. Genetic counseling and testing for Huntington’s disease: A historical review. Am J Med Genet B Neuropsychiatr Genet. 2017;174(1):75–92.

    Article  Google Scholar 

  12. Roberts JS, Uhlmann WR. Genetic susceptibility testing for neurodegenerative diseases: ethical and practice issues. Prog Neurobiol. 2013;110:89–101.

    Article  Google Scholar 

  13. Payne K, Walls B, Wojcieszek J. Approach to assessment of Parkinson disease with emphasis on genetic testing. Med Clin North Am. 2019;103(6):1055–75.

    Article  Google Scholar 

  14. Goldman JS. Genetic testing and counseling in the diagnosis and management of young-onset dementias. Psychiatr Clin North Am. 2015;38(2):295–308.

    Article  Google Scholar 

  15. Verbrugge J, Cook L, Miller M, Rumbaugh M, Schulze J, Heathers L, et al. Outcomes of genetic test disclosure and genetic counseling in a large Parkinson’s disease research study. J Genet Couns. 2020. https://doi.org/10.1002/jgc4.1366.

  16. In-person find a genetic counselor. The National Society of Genetic Counselors. 2020. Available from: https://www.nsgc.org/findageneticcounselor. Accessed April 6, 2020.

  17. Unim B, Pitini E, Lagerberg T, Adamo G, De Vito C, Marzuillo C, et al. Current genetic service delivery models for the provision of genetic testing in Europe: a systematic review of the literature. Front Genet. 2019;10:552.

    Article  Google Scholar 

  18. Alcalay RN, Kehoe C, Shorr E, Battista R, Hall A, Simuni T, et al. Genetic testing for Parkinson disease: current practice, knowledge, and attitudes among US and Canadian movement disorders specialists. Genet Med. 2019;4.

  19. Harbo HF, Finsterer J, Baets J, Van Broeckhoven C, Di Donato S, Fontaine B, et al. EFNS guidelines on the molecular diagnosis of neurogenetic disorders: general issues, Huntington’s disease, Parkinson’s disease and dystonias. Eur J Neurol. 2009;16(7):777–85.

    Article  CAS  Google Scholar 

  20. Cook L, Schulze J. Connecting Gaucher and Parkinson disease: considerations for clinical and research genetic counseling settings. J Genet Couns. 2017;26(6):1165–72.

    Article  Google Scholar 

  21. New Genetic Associations for Parkinson’s Disease Identified [Internet]. 23andMe Blog. 2017. Available from: https://blog.23andme.com/23andme-research/new-genetic-associations-parkinsons-disease-identified/. Accessed April 6, 2020.

  22. Shiner T, Mirelman A, Gana Weisz M, Bar-Shira A, Ash E, Cialic R, et al. High frequency of GBA gene mutations in dementia with Lewy bodies among Ashkenazi Jews. JAMA Neurol. 2016;73(12):1448–53.

    Article  Google Scholar 

  23. Lythe V, Athauda D, Foley J, Mencacci NE, Jahanshahi M, Cipolotti L, et al. GBA-associated Parkinson’s disease: progression in a deep brain stimulation cohort. J Parkinsons Dis. 2017;7(4):635–44.

    Article  CAS  Google Scholar 

  24. Ligaard J, Sannæs J, Pihlstrøm L. Deep brain stimulation and genetic variability in Parkinson’s disease: a review of the literature. NPJ Parkinsons Dis. 2019;5:18.

    Article  Google Scholar 

  25. Di Fonzo A, Monfrini E, Erro R. Genetics of movement disorders and the practicing clinician: who and what to test for? Curr Neurol Neurosci Rep. 2018;18(7):37.

    Article  Google Scholar 

  26. Sardi SP, Cedarbaum JM, Brundin P. Targeted therapies for Parkinson’s disease: from genetics to the clinic. Mov Disord. 2018;33(5):684–96.

    Article  Google Scholar 

  27. Schneider SA, Alcalay RN. Precision medicine in Parkinson’s disease: emerging treatments for genetic Parkinson’s disease. J Neurol. 2020;267(3):860–9.

    Article  CAS  Google Scholar 

  28. Turrini M, Prainsack B. Beyond clinical utility: the multiple values of DTC genetics. Appl Transl Genom. 2016;8:4–8.

    Article  Google Scholar 

  29. Falcone DC, Wood EM, Xie SX, Siderowf A, Van Deerlin VM. Genetic testing and Parkinson disease: assessment of patient knowledge, attitudes, and interest. J Genet Couns. 2011;20(4):384–95.

    Article  Google Scholar 

  30. Maloney KA, Alaeddin DS, von Coelln R, Dixon S, Shulman LM, Schrader K, et al. Parkinson’s disease: patients’ knowledge, attitudes, and interest in genetic counseling. J Genet Couns. 2018;27(5):1200–9.

    Article  Google Scholar 

  31. Hippman C, Ringrose A, Inglis A, Cheek J, Albert AYK, Remick R, et al. A pilot randomized clinical trial evaluating the impact of genetic counseling for serious mental illnesses. J Clin Psychiatry. 2016;77(2):e190–8.

    Article  Google Scholar 

  32. Moldovan R, Pintea S, Austin J. The efficacy of genetic counseling for psychiatric disorders: a meta-analysis. J Genet Couns. 2017;26(6):1341–7.

    Article  Google Scholar 

  33. Gupte M, Alcalay RN, Mejia-Santana H, Raymond D, Saunders-Pullman R, Roos E, et al. Interest in genetic testing in Ashkenazi Jewish Parkinson’s disease patients and their unaffected relatives. J Genet Couns. 2015;24(2):238–46.

    Article  Google Scholar 

  34. Scuffham TM, McInerny-Leo A, Ng S-K, Mellick G. Knowledge and attitudes towards genetic testing in those affected with Parkinson’s disease. J Community Genet. 2014 Apr;5(2):167–77.

    Article  Google Scholar 

  35. Austin J, Semaka A, Hadjipavlou G. Conceptualizing genetic counseling as psychotherapy in the era of genomic medicine. J Genet Couns. 2014;23(6):903–9.

    Article  Google Scholar 

  36. Direct-to-consumer genetic testing. BMJ. 2019. Available from: jhttps://www.bmj.com/content/367/bmj.l5688. Accessed April 6, 2020

  37. Tandy-Connor S, Guiltinan J, Krempely K, LaDuca H, Reineke P, Gutierrez S, et al. False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care. Genet Med. 2018;20(12):1515–21.

    Article  Google Scholar 

  38. Weedon MN, Jackson L, Harrison JW, Ruth KS. Very rare pathogenic genetic variants detected by SNP-chips are usually false positives: implications for direct-to-consumer genetic testing | bioRxiv [Internet]. [cited 2020 Mar 12]. Available from: https://www.biorxiv.org/content/10.1101/696799v1

  39. Badalato L, Kalokairinou L, Borry P. Third party interpretation of raw genetic data: an ethical exploration. Eur J Hum Genet. 2017;25(11):1189–94.

    Article  Google Scholar 

  40. Pitini E, D’Andrea E, De Vito C, Rosso A, Unim B, Marzuillo C, et al. A proposal of a new evaluation framework towards implementation of genetic tests. PLoS One. 2019;14(8):e0219755. Published 2019 Aug 5. https://doi.org/10.1371/journal.pone.0219755.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Cohen SA, Bradbury A, Henderson V, Hoskins K, Bednar E, Arun BK. Genetic counseling and testing in a community setting: quality, access, and efficiency. Am Soc Clin Oncol Educ Book. 2019;39:e34–44.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Medical and Molecular Genetics/Hereditary Genomics Division, Indiana University School of Medicine, 410 West 10th Street, Indianapolis, IN, 46202-3002, USA

    Lola Cook & Jeanine Schulze

  2. Parkinson’s Foundation, Miami, FL, USA

    Anna Naito

  3. Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA

    Roy N. Alcalay

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  1. Lola Cook
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  2. Jeanine Schulze
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  4. Roy N. Alcalay
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Corresponding author

Correspondence to Lola Cook.

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Conflict of Interest

Roy N. Alcalay’s research is supported by the NIH, the DoD, the Parkinson’s Foundation, and the Michael J. Fox Foundation. He has received consultation fees from Genzyme/Sanofi, Restorbio and Roche. L. Cook, J. Schulze, C., and A. Naito report no disclosures relevant to the manuscript.

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This Article is part of the Topical Collection on Movement Disorders

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Cook, L., Schulze, J., Naito, A. et al. The Role of Genetic Testing for Parkinson’s Disease. Curr Neurol Neurosci Rep 21, 17 (2021). https://doi.org/10.1007/s11910-021-01100-7

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