Whole-genome sequencing--issues and recommendations

As regular readers of this blog know, I get alerts every day on genetic testing, gentics, etc. and read through those for ideas for this blog. I generally choose ones that are of interest to me and I hope to those reading Genetizen. Unfortunately, some of the alerts relate to professional publications which many of you cannot access. When this happens, I request a reprint from the corresponding author and give you as much as I can about the article..

An article titled, Research ethics and the challenge of whole-genome sequencing, an advanced online publication of Nature Reviews Genetics 18 December 2007 struck my I've-got-to-blog-about-this bone. Timothy Caulfield, one of the authors, was kind enough to send me an electronic copy of the full article. You can obtain the same yourself if you have access to a library that carries Nature Review Genetics, a subscription, or the authors e-mail address, which I will be happy to provide in response to comments on this blog. Because of copyright issues, I cannot simply post the entire article

The article begins with an acknowledgement of the sequencing of the genomes of James Watson and Craig Venter, as well as the plans for nine more volunteers to have their genomes published when they are completed. A tenth person will have a genome sequenced, but not published for public review. As the authors state, “Privacy, confidentiality and the potential for subsequent discrimination have been identified as major considerations, but other issues remain for those . . . who have agreed to have their genomes mapped non-anonymously.” By extrapolation, I believe these issues also apply to anyone who might have whole-genome sequencing—or, probably, genetic testing of any kind.

In this blog entry, I am posting the recommendations the authors have formulated. In the next three entries, to follow one day at a time, I will discuss the issues surrounding the three main issues they discuss.

Summary of Recommendations

The authors propose specific recommendations for each of several ethically controversial issues, grouped under three headings:

Returning research results

Recommendation 1.1. All human whole-genome sequencing initiatives should be conducted under a formal research protocol, and ought to include the development of a data return and counselling policy that can be evaluated by the relevant research ethics board.

Recommendation 1.2. Further training for physicians should be provided to facilitate the communication of research results, and to provide follow-up information and clinical care as new research findings are reported.

Recommendation 1.3. Only validated data of known clinical relevance should be integrated into the health record. Practice guidelines should be developed for determining what constitutes validated and clinically relevant data. A process should be developed to update an individual’s health record with additional genetic information as research progresses and new knowledge about the clinical relevance of specific gene loci is gained.

Obligations to third-party relatives

Recommendation 2.1. During the initial informed consent process, investigators conducting human whole-genome sequencing research should discuss implications for family members and encourage participants to include close genetic relatives in decisions about research participation. As long as the risks associated with participation in genetic research can be minimized by ensuring professional integrity, maintaining confidentiality and implementing security measures to prevent unauthorized access to the data, additional informed consent from close genetic relatives should not be required.

Recommendation 2.2. In the context of data release, participants should be encouraged to notify affected family members, and investigators should take a family-centered approach to informed consent. The obligation to include at-risk relatives increases with the degree of relatedness to the primary research subject and, when inclusion is not practical, investigators ought to strongly encourage the research participant to discuss the research with his or her relatives and make a family decision about data release. The investigator should offer to help facilitate this discussion and should provide genetic counselling when appropriate. Objections from family members should be investigated by a research ethics consultation team, if available, and reviewed by the relevant ethics review board.

Recommendation 2.3. American Society of Human Genetics guidance regarding unauthorized disclosure of genetic risk to third-party relatives in the clinical context should be expanded to the research setting. As long as the data are validated, the permissibility of unauthorized disclosure will depend on the clinical relevance of the information and the potential to avert or alleviate known health risks.

Future uses

Recommendation 3.1. Policy work should focus on developing consent mechanisms that can be reconciled with existing consent norms, including the analysis of the appropriateness of a broad future-use consent model. In the meantime, genome researchers must ensure that research remains within the spirit of the original consent, or re-consenting should be considered.

Stay tuned for discussions of why these recommendations are being made.

Marie Godfrey, PhD

| | mgodfrey39's blog