Disclosing pathogenic genetic variants to research participants: Quantifying an emerging ethical responsibility
- Christopher A. Cassa1,2,3,9,
- Sarah K. Savage3,
- Patrick L. Taylor4,
- Robert C. Green2,5,6,
- Amy L. McGuire7 and
- Kenneth D. Mandl1,2,3,8
- 1Children's Hospital Informatics Program, Children's Hospital Boston, Boston, Massachusetts 02115, USA;
- 2Harvard Medical School, Harvard University, Boston, Massachusetts 02115, USA;
- 3Children's Hospital Boston, Boston, Massachusetts 02115, USA;
- 4Petrie-Flom Center of Harvard Law School, Cambridge, Massachusetts 02138, USA;
- 5Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 6Partners Healthcare Center for Personalized Genetic Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 7Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, Texas 77030, USA;
- 8Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA
Abstract
There is an emerging consensus that when investigators obtain genomic data from research participants, they may incur an ethical responsibility to inform at-risk individuals about clinically significant variants discovered during the course of their research. With whole-exome sequencing becoming commonplace and the falling costs of full-genome sequencing, there will be an increasingly large number of variants identified in research participants that may be of sufficient clinical relevance to share. An explicit approach to triaging and communicating these results has yet to be developed, and even the magnitude of the task is uncertain. To develop an estimate of the number of variants that might qualify for disclosure, we apply recently published recommendations for the return of results to a defined and representative set of variants and then extrapolate these estimates to genome scale. We find that the total number of variants meeting the threshold for recommended disclosure ranges from 3955–12,579 (3.79%–12.06%, 95% CI) in the most conservative estimate to 6998–17,189 (6.69%–16.48%, 95% CI) in an estimate including variants with variable disease expressivity. Additionally, if the growth rate from the previous 4 yr continues, we estimate that the total number of disease-associated variants will grow 37% over the next 4 yr.
Footnotes
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↵9 Corresponding author.
E-mail cassa{at}alum.mit.edu.
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.127845.111.
- Received June 16, 2011.
- Accepted November 23, 2011.
- Copyright © 2012 by Cold Spring Harbor Laboratory Press
Freely available online through the Genome Research Open Access option.