Ethical and Community Issues Raised by the International HapMap Project

Ethical and Community Issues Raised by the International HapMap Project

The International HapMap Consortium devoted considerable time and resources to try to ensure that the map was designed, developed and will be used in a manner that is sensitive to a wide range of ethical and social issues.

Following the example set by the Human Genome Project, the International HapMap Project established a group of bioethicists and social and behavioral scientists, who worked alongside genomic researchers, to formulate important aspects of this large, complex study. These issues included: how to design a scientifically valid sampling strategy, engage the individuals and communities that were approached to donate samples, decide how the populations would be described, and develop understanding of the HapMap in order to maximize its benefits in current and future studies.

This group, co-chaired by Ellen Wright Clayton, M.D., J.D., of Vanderbilt University and Bartha Knoppers, J.D., Ph.D. of the University of Montreal, included members from each participating country. For a complete list of members, see Ethical, Legal and Social Implications Group [hapmap.ncbi.nlm.nih.gov].

Sampling Strategy

The HapMap is a powerful medical research tool intended to speed the discovery of genetic contributions to common diseases. The HapMap, which describes the common patterns of human genetic variation, can be used in studies that compare the patterns of genetic variation (haplotypes) in people with a specific disease to patterns in people without the disease. By identifying regions of the genome that show differences in the haplotype patterns, researchers can home in on those genomic regions to more efficiently find the particular genetic variants that contribute to the disease.

To produce the HapMap, researchers analyzed blood samples from a total of 269 people from four large populations These populations are: Yoruba in Ibadan, Nigeria; Japanese in Tokyo; Han Chinese in Beijing; and Utah residents with ancestry from northern and western Europe.

These four populations were selected to include people with ancestry from widely separate geographic regions. Researchers have found that most human populations share the common haplotype patterns and the overall organization of genetic variation is very similar. There are differences in the frequencies of some haplotypes, however, so it was useful to include samples from several populations and to identify where each set of samples originated. Still, none of the four populations sampled should be considered representative of all populations on the same continent.

Except for the Utah samples, all of the samples were newly collected for this project. The Utah samples, which have already been studied for many other genetic research projects, were used only after the donors provided a new and specific consent for the HapMap Project.

Privacy and Informed Consent

The HapMap raises few risks to the privacy of individual donors because the blood samples used to make the resource were collected without any medical or personally identifying information. In a further step to ensure the complete anonymity of the donors, the consortium collected more samples than were actually used. That means that no one, not even the donors themselves, will ever know for sure whose samples were used to develop the HapMap.

However, each set of samples is identified by population to facilitate the selection of optimal markers of genetic variation, called tag SNPs, in future studies searching for genes in specific populations. This labeling raises complex ethical issues because such studies have the potential to affect all members of a population, as well as members of closely related populations, even though they did not personally donate samples for the HapMap. For this reason, processes were implemented to identify, understand and, to the fullest extent possible, address the concerns of both individuals and groups being approached for sample donation.

The goal of the individual consent process was to provide prospective sample donors with the information they needed to ensure their decisions about whether to donate a blood sample were voluntary and informed. All donors were asked to give consent for their samples to be used not just for the HapMap itself, but in many types of future genetic variation studies. Such studies may examine how genes are regulated, the biology of DNA, how new variations arise and the genetic history of human groups. Researchers explained to donors that the benefits of the HapMap and of other genetic variation research may not become apparent for some time and that the donors themselves may not benefit directly. For more information about the consent process, go to Consent Forms [hapmap.ncbi.nlm.nih.gov].

Community Engagement

Before obtaining informed consent from individual donors, researchers initiated a process of community engagement. The goal of this process was to give a broad range of community members in each locality where people were being approached to donate samples the opportunity to share their views about the ethical, social and cultural issues the project raised for themselves, their families, their immediate communities and the broader populations to which they belong.

Each community where new samples were collected also had input into how samples from their community would be identified. Thoughtful labeling will help reduce the risk that findings based on HapMap data will be over-generalized. For the complete guidelines on referring to HapMap populations, see Guidelines for Referring to the HapMap Populations in Publications and Presentations [hapmap.ncbi.nlm.nih.gov].

In addition, a community advisory group (CAG) was established in each community where new samples were collected to ensure that all future research using the samples is consistent with the terms of the informed consent. The non-profit Coriell Institute for Medical Research in Camden, N.J., which is storing and distributing the samples, will report on a quarterly basis to each community.

Each quarterly report will provide the communities with a list of researchers to whom the samples have been distributed and the nature of the research for which the samples are being used. In addition, the report will include information about scientific papers published by the HapMap consortium and by other researchers who have conducted studies that used HapMap data or samples.

Free, periodic newsletters, translated into the languages of all participating communities, will provide both communities and the general public with additional information about the HapMap Project, the uses of the HapMap and the participating communities themselves. The newsletters are available at: International HapMap Resource [ccr.coriell.org].

Genetic Discrimination and Determinism

Because researchers did not collect medical or personally identifying information, there is virtually no risk that the HapMap itself will lead to discrimination against any of the individual sample donors.

However, in future studies, some genetic variants are likely to be identified that promote wellness and protect against disease, while other variants will be identified that increase the risk for particular diseases. If a higher frequency of a genetic variant associated with a particular disease is found in the samples from one population and the findings are erroneously assumed to apply to most or all members of that group, the potential for stereotyping or discrimination may arise.

Although the HapMap was created as a tool for medical research, researchers in other fields, such as anthropology, may use the genetic variation data contained in the HapMap to facilitate their studies of human history and the relatedness of human populations. Some groups may find such studies problematic, especially as they relate to traditional notions of race and ethnicity.

Another problem with the interpretation of genetic variation is assuming that "genetic" means "unchangeable," and that because someone has a particular genetic variant they are "doomed" to get the disease. These incorrect assumptions are called genetic determinism. Genetic determinism overlooks the strong contributions that environmental factors make to diseases and that there may be ways to reduce the risk of getting those diseases. So, even though people may have genetic variants contributing to their risk of a disease, many of them will never get the disease.

Genetic discrimination and genetic determinism are problems that may arise from any association study relating genetic variation to disease risk and are not unique to studies that will use the HapMap. Nevertheless, the HapMap consortium is making concerted efforts to reduce the risk of such problems by educating researchers on how to carefully design their studies and describe their results.