Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Return of genetic testing results in the era of whole-genome sequencing

Abstract

Genetic testing based on whole-genome sequencing (WGS) often returns results that are not directly clinically actionable as well as raising the possibility of incidental (secondary) findings. In this article, we first survey the laws and policies guiding both researchers and clinicians in the return of results for WGS-based genetic testing. We then provide an overview of the landscape of international legislation and policies for return of these results, including considerations for return of incidental findings. Finally, we consider a range of approaches for the return of results.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

References

  1. Hall, A., Finnegan, T. & Alberg, C. Realising genomics in clinical practice. PHG Foundation [online], (2014).

    Google Scholar 

  2. Wade, C. H., Tarini, B. A. & Wilfond, B. S. Growing up in a genomic era: implications of whole-genome sequencing for children, families, and pediatric practice. Annu. Rev. Genomics Hum. Genet. 14, 535–555 (2013).

    Article  CAS  Google Scholar 

  3. Richards, S. 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. 17, 405–423 (2015).

    Article  Google Scholar 

  4. Zawati, M. H. & Knoppers, B. M. International normative perspectives on the return of individual research results and incidental findings in genomic biobanks. Genet. Med. 14, 484–489 (2012).

    Article  Google Scholar 

  5. Parliament of Estonia. Human Genes Research Act. Estonia Legal Text [online], (2000).

  6. Parliament of Spain. Law 14/2007 of 3 July on Biomedical Research. Instituto de Salud Carlos III [online], (2007).

  7. Parliament of Taiwan. Human Biobank Management Act. Laws and regulations database of the republic of China. Laws & Regulations Database of The Republic of China [online], (2010).

  8. Parliament of Finland. Biobank Act 688/2012. Finland Ministry of Social Affairs and Health [online], (2012).

  9. ACMG Board of Directors. ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing. Genet. Med. 17, 68–69 (2015).

  10. Boycott, K. et al. The clinical application of genome-wide sequencing for monogenic diseases in Canada: position statement of the Canadian College of Medical Geneticists. J. Med. Genet. 52, 431–437 (2015).

    Article  CAS  Google Scholar 

  11. Knoppers, B. M., Avard, D., Sénécal, K., Zawati, M. H. & P3G International Paediatrics Platform Members. Return of whole-genome sequencing results in paediatric research: a statement of the P3G international paediatrics platform. Eur. J. Hum. Genet. 22, 3–5 (2014).

    Article  CAS  Google Scholar 

  12. Ethical Advisory Group of the UK10K Project. Ethical governance framework. UK10K[online], (2010).

  13. Danish Council of Ethics. Genome testing: ethical dilemmas in relation to diagnostics, research and direct-to consumer testing. Danish Council of Ethics [online], (2012).

  14. World Medical Association. WMA declaration of Helsinki — ethical principles for medical research involving human subjects. WMA[online], (2013).

  15. United Nations Educational, Scientific and Cultural Organization. Universal declaration on the human genome and human rights. UNESCO[online], (1997).

  16. Council of Europe. Convention for the protection of human rights and dignity of the human being with regard to the application of biology and medicine: convention on human rights and biomedicine. Council of Europe Treaty Office [online], (1997).

  17. Medical Research Council. Framework on the feedback of health-related findings in research. Wellcome Trust[online], (2014).

  18. Hall, A., Hallowell, N. & Zimmern, R. Managing Incidental and Pertinent Findings from WGS in the 100,000 Genomes Project. PHG Foundation[online], (2013).

  19. Wright, C. et al. Next steps in the sequence: the implications of whole genome sequencing for health. PHG Foundation[online], (2011).

  20. Thorogood, A., Joly, Y. & Knoppers, B. M. An implementation framework for the feedback of individual research results and incidental findings in research. BMC Med. Ethics 15, 1–13 (2014).

    Google Scholar 

  21. Zawati, M. H. & Rioux, A. Biobanks and the return of research results: out with the old and in with the new? J. Law Med. Ethics 39, 614–620 (2011).

    Article  Google Scholar 

  22. Kass, N. E. et al. The research-treatment distinction: a problematic approach for determining which activities should have ethical oversight. Hastings Cent. Rep. 43, S4–S15 (2013).

    Article  Google Scholar 

  23. Thorogood, A. et al. Whole-genome sequencing and the physician. Clin. Genet. 81, 511–513 (2012).

    Article  CAS  Google Scholar 

  24. Saunders, C. J. et al. Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units. Sci. Transl Med. 4, 154a135 (2012).

    Article  Google Scholar 

  25. Weiner, C. Anticipate and communicate. Ethical management of incidental and secondary findings in the clinical, research, and direct-to-consumer contexts (December 2013 report of the Presidential Commission for the Study of Bioethical Issues). Am. J. Epidemiol. 180, 562–564 (2013).

    Article  Google Scholar 

  26. American College of Medical Genetics and Genomics. ACMG updates recommendation on “opt out” for genome sequencing return of results. ACMG News[online], (2014).

  27. German National Ethics Council. The future of genetic diagnosis — from research to clinical practice. Deutscher Ethikrat[online], (Germany, 2013).

  28. Zawati, M. H., Parry, D. & Knoppers, B. M. The best interests of the child and the return of results in genetic research: international comparative perspectives. BMC Med. Ethics 15, 72 (2014).

    Article  Google Scholar 

  29. Whorthey, E. A. Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet. Med. 13, 255–262 (2011).

    Article  Google Scholar 

  30. Mayer, A. N. et al. A timely arrival for genomic medicine. Genet. Med. 13, 195–196 (2011).

    Article  Google Scholar 

  31. Mendel's Pod. Father/scientist finds gene responsible for daughter's unknown syndrome: Hugh Rienhoff talks personal genomics. Mendel's Pod[online]

  32. Goh, V. et al. Next-generation sequencing facilitates the diagnosis in a child with twinkle mutations causing cholestatic liver failure. J. Pediatr. Gastroenterol. Nutr. 54, 291–294 (2012).

    Article  Google Scholar 

  33. Hawcutt, D. B. et al. Paediatric pharmacogenomics: an overview, Arch. Dis. Child. 98, 232–237 (2013).

    Article  Google Scholar 

  34. Steven, A. et al. Pediatric perspective on pharmacogenomics. Pharmacogenomics. 14, 1889–1905 (2013).

    Article  Google Scholar 

  35. Amor, D. J. Future of whole genome sequencing. J. Paediatr. Child Health. 51, 251–254 (2014).

    Article  Google Scholar 

  36. Green, R. C. et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet. Med. 15, 565–574 (2013).

    Article  CAS  Google Scholar 

  37. Botkin, J. R. et al. Points to consider: ethical, legal, and psychological implications of genetic testing in children and adolescents. Am. J. Hum. Genet. 97, 6–21 (2015).

    Article  CAS  Google Scholar 

  38. van El, C. G. et al. Whole-genome sequencing in health care. Recommendations of the European Society of Human Genetics. Eur. Soc. Hum. Genet. 21 (Suppl. 1), 1–5 (2013).

    Google Scholar 

  39. Hens, K. et al. Developing a policy for paediatric biobanks: principles for good practice. Eur. J. Hum. Genet. 21, 2–7 (2013).

    Article  Google Scholar 

  40. Knoppers, B. M., Sénécal, K., Borry, P. & Avard, D. Whole genome sequencing in newborn screening programs. Sci. Transl Med. 6, 229cm2 (2014).

    Article  Google Scholar 

  41. Howard, H. C. et al. Whole genome sequencing in newborn screening? A statement on the continued importance of targeted approach in newborn screening programmes. Eur. J. Hum. Genet. http://dx.doi.org/10.1038/ejhg.2014.289 (2015).

  42. Paxton, A. Next-gen shifts DNA sequencing into hyperdrive. CAP Today[online], (2011).

  43. Knoppers, B. M., Deschênes, M., Zawati, M. H. & Tassé, A. M. Population studies: return of research results and incidental findings policy statement. Eur. J. Hum. Genet. 21, 245–247 (2013).

    Article  Google Scholar 

  44. ACMG Board of Directors. Points to consider in the clinical application of genomic sequencing. Genet. Med. 14, 759–761 (2012).

  45. ACMG Board of Directors. Points to consider for informed consent for genome/exome sequencing. Genet. Med. 15, 748–749 (2013).

  46. American College of Medical Genetics and Genomics. Incidental findings in clinical genomics: a clarification. Genet. Med. 15, 664–666 (2013).

  47. Gutmann, A. Privacy and progress in whole genome sequencing. Presidential Commission for the Study of Bioethical Issues [online], (2012).

    Google Scholar 

Download references

Acknowledgements

The authors thank E. Kleiderman and A. Pack (from the Centre of Genomics and Policy) for their assistance. In addition, the authors thank the Ministère de l'Économie, l'Innovation et des Exportations du Québec; the Fonds de Recherche du Québec; the Network of Applied Genetic Medicine of Québec; and Care4Rare Canada Consortium funded by Genome Canada, the Canadian Institutes of Health Research, the Ontario Genomics Institute, Ontario Research Fund, Genome Quebec and Children's Hospital of Eastern Ontario Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bartha Maria Knoppers.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Knoppers, B., Zawati, M. & Sénécal, K. Return of genetic testing results in the era of whole-genome sequencing. Nat Rev Genet 16, 553–559 (2015). https://doi.org/10.1038/nrg3960

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg3960

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing