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Journal Publication Editorial

November 2001

“The findings and conclusions in this report are those of the author(s) and do not necessarily represent the views of the funding agency."

Informed Consent for Population Research Involving Genetics:
A Public Health Perspective

Muin Khoury, MD, PhD, Director,
Office of Genomics and Disease Prevention, Centers for Disease Control and Prevention

In February 2001, the initial analysis of the human genome sequence was published.   Soon we will know the sequence of the approximately 50,000 human genes. More than 10,000 of these genes have already been discovered that relate to many diseases, and more than 870 genetic tests are currently available.  Nevertheless, most genes that have been discovered and most tests that are available pertain to single gene conditions (the so called genetic diseases). These conditions are individually rare and have limited public health impact, although collectively they do account for about 5% of human disease.

The real promise of genomics and its public health impact will be our improved ability to use genetic information in diagnosing, treating, and preventing the other 95% of human diseases, diseases that we normally do not think of as “genetic” that are due to complex interactions between multiple genes and the environment. (We define the environment broadly to include infectious, chemical, nutritional, and social factors.) For these diseases, we will be looking at genes that code for blood groups, immune antigens such as the HLA system, enzymes involved in metabolism of drugs and carcinogens, and many other genes for which population variation is common. Health outcomes associated with these variants include the bulk of chronic diseases, such as heart disease and cancer, that are the top leading causes of death in this country.

As we ponder this simple question—the human genome is mapped: now what—we realize that the impact of common genetic variants on the health and well being of the population has not been evaluated. To ensure the appropriate use of genetic information, we now face the important challenge of conducting population-based epidemiologic research that ultimately will allow us to integrate genetics into disease treatment and prevention. This research will focus on  the prevalence of gene variants in different populations, the burden of diseases, the impact of gene-gene and gene-environment interaction on disease risk, as well as the validity and utility of genetic tests in improving population health.

As in other areas of public health, it is crucial that population research involving genetics be done in an ethical framework with informed consent of study participants. Much has been written about ethical issues in epidemiology; ethical, legal, and social issues in genetic testing; and informed consent for clinical genetic research. However, little or no guidance is available specifically for population-based studies of common gene variants with low to moderate individual disease risks. Recommendations developed for family-based research are not well suited for most population-based studies because these recommendations generally fail to distinguish between those studies expected to reveal clinically relevant information about participants from studies expected to have meaningful public health implications but that involve few physical, psychological, or social risks for individual participants. Uniform application of these recommendations to all genetic research could make some otherwise beneficial population-based studies difficult or impossible to conduct. As noted by Clayton et al. in a 1995 JAMA expert panel article  “the risks involved in identifying high-risk mutations must be distinguished from the risks of identifying ‘common alleles that are neither necessary nor sufficient for the development of disease.'"

In response to the need for appropriate guidelines, the Centers for Disease Control and Prevention formed a multidisciplinary working group to develop an informed consent approach needed for integrating genetic variation into population-based research.  Although the recommendations of this group do not represent government policy, they are meant to stimulate discussion and dialogue and to suggest issues to consider for research sponsors, institutional review boards, and investigators.  The group used expert opinion as well as federal regulations, the National Bioethics Advisory Commission's report on research involving human biological materials, existing consent forms, and literature on informed consent to create suggested language and points to consider for informed consent documents and a supplemental brochure.   The language of the recommendations reflects the premise that the probability and magnitude of harm—as well as possible personal benefits—are directly related to the meaning of the results for the health of the participant and that appropriate disclosures and processes for obtaining consent should be based at the outset on an assessment of the likelihood that the results will generate information that could lead directly to an evidence-based intervention.

The informed consent template contains suggested language for informed consent required by ethical considerations and federal regulations. The supplemental brochure provides answers to questions that prospective participants in population-based research involving genetics are likely to ask, such as: Why is this study being done? What is involved in this study? How will information about me be kept private? What are the risks of the study?  Are any costs or payment involved? How will I find out about the results of the study?

We are in the infancy of the "genetic revolution" and much is unknown. Establishing associations between genes and disease in the general population begins with quantifying statistical relations, and even those relations that appear to be significant cannot be applied to particular individuals. As in other epidemiologic research, the interpretation of such data requires replication of findings from other studies. In addition, many population-based genetic studies will focus on gene variants associated with low individual risk of disease (low penetrance). Family-based studies provide a unique framework for investigating gene variants with high disease risk (high penetrance). Low penetrance gene variants lead to smaller increases in relative risk for disease and to a corresponding decrease in the probability of harm stemming from misuse of the information. Research on low-penetrance gene variants may, however, allow better understanding of disease mechanisms and the role of environmental exposures on a population level and can provide significant opportunities for public health intervention.

There will be population-based studies for which the approach suggested by the working group is not appropriate. An example of this would be when previous studies have suggested strong gene-disease association or gene-environment interaction and researchers postulate some clinical value to individuals as a result of their study. Thus, the decision to use the approach suggested by the working group should be based at the outset on an assessment of the likelihood that research results will generate information that could lead directly to an evidence-based intervention.

The proposed approach is not fundamentally different from existing guidance for other kinds of public health research; rather it is an extension of these guidelines.  The suggested language applies when studies are exploratory in nature, as is currently typical of much population-based research involving genetics. Our ultimate challenge is to determine the benefits of using genetic information to target interventions that improve health and prevent disease. For that, we must acknowledge that gene discovery is only the beginning and that there is a crucial role for population research to fulfill the promise of the human genome project for citizens of the 21st century.

Page last reviewed: June 8, 2007 (archived document)
Page last updated: September 10, 2007
Content Source: National Office of Public Health Genomics
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