Insights about disease risks gleaned from a person's genome sequence can be relevant not only to that individual, but also to his or her relatives. People participating in studies that yield clinically important information therefore often decide to share their results with family members. But what if the participant dies before he or she receives the results?
A study in the American Journal of Bioethics by members of the National Human Genome Research Institute's ClinSeq study addresses this issue.
ClinSeq, a large-scale medical sequencing study that has about 1,000 individuals enrolled, analyzes the exomes or genomes of participants and returns clinically significant results to them.
So far, ClinSeq investigators have become aware of three cases where participants have died, prompting them to consider whether to return results to their relatives.
The first case came to light in 2010, when the ClinSeq team tried to follow up with a participant who had enrolled two years earlier, but had since died. At the time of the follow-up, exome sequencing and a partial analysis of his genome had been performed, but he had not received any results.
After talking to the NIH Clinical Center's Bioethics Consultation Service, the ClinSeq team contacted one of the participant's sons, the executor of his estate, who they decided would serve as their point of contact for the family. He expressed "much interest" in learning about his father's results and said that his sister would also be interested.
The research team concluded that there was good reason to return certain results to this participant's family, as they might have a bearing on their health and as family members had expressed an interest in receiving them. But it was not immediately clear which results should be returned and to whom and how they should be disclosed.
With regard to the nature of information to be returned, the ClinSeq team decided that they should only include variants with well-established clinical significance, meaning variants "linked to a significant harm" where "there are measures that one can take to prevent or treat the potential harm."
To actual ClinSeq participants, the researchers might return a wider range of results, but when a research subject dies, "we shift more to a mode of clinical utility and say to ourselves, 'What are the variants that are of the highest potential utility, medically actionable things that would be prudent to disclose to a person, whether they were a research subject or not?' And of course that's a much smaller set of results than the larger set that the research subject probands would get," says Les Biesecker, ClinSeq's principal investigator and chief of the genetic disease research branch at NHGRI.
Which specific results would be returned to relatives would be decided on a case-by-case basis, he adds.
The team further decided that a single member of the deceased participant's family — usually the executor of his or her estate — should decide on obtaining results and receive them on behalf of the family.
This family member would then receive the information in the same way that ClinSeq participants currently do, which involves making a separate decision on each clinically significant finding and a face-to-face consultation with a genetic counselor.
ClinSeq would not be involved in testing or follow-up treatment of relatives.