Disclosing pathogenic genetic variants to research participants: Quantifying an emerging ethical responsibility
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 com...
| Main Authors: | , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Cold Spring Harbor Laboratory Press
2013
|
| Online Access: | http://hdl.handle.net/1721.1/76767 |
| _version_ | 1826195529677144064 |
|---|---|
| author | Cassa, Christopher A. Savage, Sarah K. Taylor, Patrick L. Green, Robert C. McGuire, Amy L. Mandl, Kenneth D. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Cassa, Christopher A. Savage, Sarah K. Taylor, Patrick L. Green, Robert C. McGuire, Amy L. Mandl, Kenneth D. |
| author_sort | Cassa, Christopher A. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:14:10Z |
| format | Article |
| id | mit-1721.1/76767 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:14:10Z |
| publishDate | 2013 |
| publisher | Cold Spring Harbor Laboratory Press |
| record_format | dspace |
| spelling | mit-1721.1/767672022-09-30T19:48:13Z Disclosing pathogenic genetic variants to research participants: Quantifying an emerging ethical responsibility Cassa, Christopher A. Savage, Sarah K. Taylor, Patrick L. Green, Robert C. McGuire, Amy L. Mandl, Kenneth D. Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Civil and Environmental Engineering Cassa, Christopher A. McGuire, Amy L. Mandl, Kenneth D. 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. National Library of Medicine (U.S.) (grant LM010470-01) Boston Children's Hospital. Manton Center for Orphan Disease Research Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (training grant HD040128) Baylor College of Medicine (BCM Clinical and Translational Research program) Baylor College of Medicine (Baylor Annual Fund) Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (AG027841) Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (HG02213) Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (HG005092) 2013-02-07T20:23:57Z 2013-02-07T20:23:57Z 2011-12 2011-06 Article http://purl.org/eprint/type/JournalArticle 1088-9051 http://hdl.handle.net/1721.1/76767 Cassa, C. A. et al. “Disclosing Pathogenic Genetic Variants to Research Participants: Quantifying an Emerging Ethical Responsibility.” Genome Research 22.3 (2011): 421–428. Web.© 2012 by Cold Spring Harbor Laboratory Press. en_US http://dx.doi.org/10.1101/gr.127845.111 Genome Research Creative Commons Attribution Non-Commercial http://creativecommons.org/licenses/by-nc/3.0 application/pdf Cold Spring Harbor Laboratory Press Genome Research |
| spellingShingle | Cassa, Christopher A. Savage, Sarah K. Taylor, Patrick L. Green, Robert C. McGuire, Amy L. Mandl, Kenneth D. Disclosing pathogenic genetic variants to research participants: Quantifying an emerging ethical responsibility |
| title | Disclosing pathogenic genetic variants to research participants: Quantifying an emerging ethical responsibility |
| title_full | Disclosing pathogenic genetic variants to research participants: Quantifying an emerging ethical responsibility |
| title_fullStr | Disclosing pathogenic genetic variants to research participants: Quantifying an emerging ethical responsibility |
| title_full_unstemmed | Disclosing pathogenic genetic variants to research participants: Quantifying an emerging ethical responsibility |
| title_short | Disclosing pathogenic genetic variants to research participants: Quantifying an emerging ethical responsibility |
| title_sort | disclosing pathogenic genetic variants to research participants quantifying an emerging ethical responsibility |
| url | http://hdl.handle.net/1721.1/76767 |
| work_keys_str_mv | AT cassachristophera disclosingpathogenicgeneticvariantstoresearchparticipantsquantifyinganemergingethicalresponsibility AT savagesarahk disclosingpathogenicgeneticvariantstoresearchparticipantsquantifyinganemergingethicalresponsibility AT taylorpatrickl disclosingpathogenicgeneticvariantstoresearchparticipantsquantifyinganemergingethicalresponsibility AT greenrobertc disclosingpathogenicgeneticvariantstoresearchparticipantsquantifyinganemergingethicalresponsibility AT mcguireamyl disclosingpathogenicgeneticvariantstoresearchparticipantsquantifyinganemergingethicalresponsibility AT mandlkennethd disclosingpathogenicgeneticvariantstoresearchparticipantsquantifyinganemergingethicalresponsibility |