Genome sequencing--obligations to close relatives

This is part 2 of the discussion of the issues raised in the Nature Reviews Genetics article, Research ethics and the challenge of whole-genome sequencing. The article itself is available only to those with library access or a journal subscription. As in earlier entries, quotations and indentations identify text taken directly from the article.

I wonder. . . did James Watson or Craig Venter ask their relatives whether they agreed to them having their whole genome sequence posted for the public to see? What about the 9 volunteers for the next public batch of genome sequencing?

 Data obtained from genome sequencing reveal information not only about the individual who is the source of the DNA, but also probabilistic information about the DNA sequence of close genetic relatives. This makes it possible to identify an individual by matching his or her DNA to the sequence of a relative’s DNA. The generation of whole-genome data significantly increases the ability to match the DNA of close relatives, and to reveal predictive information about relatives’ present and future health risks. This raises important questions about what obligations, if any, are owed to the family members of individuals who consent to have their genome sequenced as part of a research protocol.

An important point to remember here is that the DNA typing we see on CSI and other television programming is not whole-genome sequencing, but even the limited number of markers used to test for a DNA match between the "criminal" and the suspect can be sufficient to implicate close relatives (parents, siblings, and offspring). In whole-genome sequencing, the full text of a person's DNA can be determined. That information absolutely identifies the individual; even twins may have minor differences in sequencing if changes have occurred in the DNA during the individual's lifetime. At the same time, the presence of a serious mutation such as Huntington's indicates that the individual's close relatives may also be at risk.

In genetic testing conducted through primary care providers or purchased over the Internet, even the small amount of genetic information available through testing can identify potential risks for relatives. A major question now is whether a primary care provider is obligated to notify close relatives if a genetic "threat" is found in a tested individual. Who knows what companies offering testing through online sources do with the information?

In a research setting, where an individual agrees to have a DNA test or genome sequencing done as part of a clinical study, for example, that individual give "informed consent" to the process. Close relatives, however, have no opportunity to give consent--informed orotherwise--so they don't get the results (even if the individual tested does), nor are they informed of potential genetic problems. We may wonder, ". . . what obligations, if any, are owed to the family members of individuals who consent to have their genome sequenced as part of a research protocol."

The authors:

. . .propose that during the initial informed consent process, investigators conducting human whole-genome sequencing research should discuss the 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 2.1).

In the matter of data release, especially to the general public via publication on an Internet site, "researchers have greater obligations to address the concerns and protect the privacy of relatives when information on family history is published".

Decisions about data release, an emerging policy norm, should therefore ideally include family members whose privacy is most at risk. However, it can be difficult to include third-party relatives in the decision-making process if they are unknown to the investigators or if the family dynamics are less than perfect.

The authors propose:

participants should be encouraged to notify affected family members, and investigators should take a family-centered approach to informed consent (an approach that has already been embraced in many research ethics guidelines) 38. 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 should 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 to facilitate this discussion and provide genetic counselling when appropriate. Objections from family members should be investigated by a research ethics consultation team, if available, and should also be reviewed by the relevant ethics review board (recommendation 2.2).

What about clinically relevant diagnostic and predictive information? The authors "recommend that the ASHG guidance regarding unauthorized disclosure of genetic risk to third-party relatives in the clinical context should be expanded to the research setting." That guidance, from the suggest that the American Society of Human Genetics (ASHG) suggests that the unauthorized disclosure of genetic risk is permitted only if “attempts to encourage disclosure on the part of the patient have failed, the harm is highly likely to occur and is serious, imminent and foreseeable, the at-risk relative(s) is identifiable and the disease is preventable, treatable or medically accepted standards indicate that early monitoring will reduce the genetic risk.”

The authors state,

These same general principles apply in the research context.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 (recommendation 2.3).

Tomorrow, issues related to future uses of samples and data.

Marie Godfrey, PhD

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