The international scientific community sequenced the human genome in 2001, thereby commencing the long and arduous task of understanding the relationships among variation in genes, environmental exposures, and human health. To date, most of the benefits of advances in genomics have been cast in individual terms, focusing primarily on clinical decision making, health care policy, and bioethics. There is, however, another important aspect of genomic science that has the potential to powerfully affect the health and well-being of populations. Known as “public health genomics,” this emerging field assesses the impact of genes and their interaction with behavior, diet, and the environment on the population’s health. The promise of public health genomics is to have practitioners and researchers accumulating data on relationships between genetic traits and diseases across populations, to use this information to develop strategies to promote health and prevent disease in populations, and to more precisely target and evaluate population-based interventions. Public health genomics is an exciting, multidisciplinary field that brings all the public health sciences to bear on the emerging challenge of interpreting the significance of genetic variation within populations and applying that knowledge in order to improve the health of the public.
Despite the vast promise of public health genomics, there is still much that must be understood before key strategies can be implemented. Our understanding of the science of genomics is incomplete, and a great deal of data gathering, statistical assessment, and research is necessary to assess the interrelationships among genes, the environment, behavior, and population health. Furthermore, there is a need to address potential health
disparities in the application of genomic knowledge and to ensure that all population subgroups have access to the benefits of genomics. No less important are the social, legal, and ethical problems that may accompany any significant application of public health genomics to the real world. Thus, while the potential for improving the public’s health is enormous, the obstacles are currently equally substantial.
The workshop, “Implications of Genomics for Public Health,” outlined many important issues and challenges to realizing the benefits of genetics and genomics for the public’s health. Dr. Gilbert Omenn, the first keynote speaker, provided a vision of the future for genomics and public health. He described key challenges, available resources, and recommendations for policies and approaches. On the second day of the conference, the keynote speaker, Dr. Alexandra Shields, discussed the challenges of translating new knowledge into improved health in ways that benefit the entire population rather than increasing health disparities. Four panels, each of which was followed by a comment session, and a final workshop summation occupied the remainder of the agenda. The first panel provided an overview of the science of genomics, whereas the second panel addressed practice issues. On day 2 the opening panel examined the public health system, biobanks, education of the public, and public health workforce capacity. The final panel addressed genomic information and its application to population health, financing and access issues, and legal and regulatory issues. James Hodge, Jr., then provided a workshop overview of lessons learned and places to go.
After the conclusion of the workshop, committee members met to discuss each presentation and commentary and to identify and prioritize issues and approaches explored during the conference. The following presents the committee’s deliberations and conclusions.1
The committee agreed that it is of primary importance to develop a coherent understanding of the scientific literature on genetics and its application to public health and health care. This requires the development of an approach to evaluating the scientific literature in order to set forth a framework for decision making about genetic evidence. Evidence can be used to motivate changes in practice, and therefore evidence is needed in the following areas:
Predispositions for the onset of disease, both discrete genetic conditions and complex, multifactorial diseases,
Efficacy of treatments for people with diseases that have important genetic components,
Behavioral and environmental interventions to reduce risk and improve health, and
Cost-effectiveness of a broad range of clinical and environmental interventions.
It may be that an approach similar to that used by the U.S. Preventive Services Task Force and the Community Services Task Force could be used to evaluate evidence of effectiveness as well as cost-effectiveness. An approach to evaluating genetic tests proposed for use in general clinical settings would
Focus initially on primary care;
Choose clinical questions that have significant health consequences, are of relatively common frequency, have excellent analytic validity, and have effective interventions available;
Develop analytic methods, including a specific literature search strategy, a way of assessing individual articles, a hierarchy of research designs, tools for assessing the quality of research, and specific links between evidence and graded conclusions; and
Develop a coherent plan for communication and dissemination of findings.
Ideally, such evaluation would take place prior to the full use of interventions in the health care and public health systems.
Evaluation of the literature would also illuminate data gaps and the kinds of research that need to be conducted. Many types of research are needed—laboratory, basic research, population-based epidemiologic and behavioral studies, clinical trials, and effectiveness research based on use in clinical settings. In particular, a more clearly developed research agenda is needed to examine the relationship between the application of genomics and population health. For example, there are currently no studies that span the genome to proteome to metabolome, especially in populations. Currently research is either just genomics or just proteomics. Research is needed to enhance our understanding of gene–environment interactions, gene–gene interactions, and “omic” representations of biologic continuums of risk. In some ways this is the difference between thinking about genetics and thinking about genomics. Instead of thinking about and investigating one gene, the focus should be on the genome, then the proteome, and all
“omics.” Research should include both large-scale and community-based participatory approaches.
We now know that the health of populations and individuals is determined by interactions among genes, socioeconomic circumstances, behavioral choices, environmental exposures, and medical care. Therefore, it is vitally important to conduct research on the interactions of these factors and their impacts on health. The results of such research would enable health care and public health practitioners to better support behavior change toward improved health outcomes.
Furthermore, there is a need to move from a focus on single-gene disorders to a new focus that addresses common complex diseases. Genetic heterogeneity must be considered in common complex diseases. A common disease phenotype may be caused by the action or interaction of a few to many genes, and in each case environmental factors may provide additional interactions. These interactions may lead to the same general clinical phenotype through many different mechanisms. The genomic approach is to stratify disease into different gene-based disorders as opposed to the public health approach directed at the common end point. It is now well known that allele frequencies for common polymorphisms in the genome can differ among ethnic groups, including disease-susceptibility alleles. Cultural practices and environmental factors may also vary among groups in ways that influence disease expression. Thus, the population burden of disease may also differ among these groups, even if underlying biological mechanisms of genetic susceptibility are the same. As a result of these two effects, preventive and intervention measures that also consider important cultural and behavioral characteristics of the population at risk may need to be tailored to specific groups.
Thus, the implications of genomics for public health require developing a new paradigm that stratifies the population into different risk groups based upon the effects of genes, gene–gene interaction, and gene–environment interactions involved in disease predisposition; these risk groups may or may not correspond to groupings based on ethnicity. This then leads to data gathering and bioinformatics2 based upon the stratified populations, which in turn informs what the health care providers tell patients, what public health professionals tell the community, and the decision health care systems make in delivering care. In such a new paradigm, the messages are more complex and are stratified on the basis of groups. Combined with these opportunities is the need to be aware of and
guard against an inappropriate use of subgrouping to increase or support existing disparities or to create new ones. A system should be created in which the population as a whole can use genomic information to improve health.
Moving from genetics to genomics, from single-gene diseases to complex diseases, and to a better understanding of gene–environment interaction requires change in the way we think about the health of individuals and the health of the population. For example, because of differences in frequencies of disease susceptibility alleles, there can be population differences in susceptibility to disease, while at the same time environmental factors may influence gene expression leading to diseases. Hypertension and G6PD deficiency in people of African ancestry is illustrative of this point; both genetic and environmental factors influence the disease. Parsing out the pieces has the potential to be a powerful aid to improving health. However, it is important to ensure that new knowledge about genomics and disease susceptibility in subgroups of the population is used to decrease health disparities, rather than allowing risk stratification to result in further discrimination and increasing health disparities such as those associated with racial groups. We need to create a system in which the population as a whole can use genomic information to improve health.
Change is also needed in the ways in which public health interventions and health information messages are delivered. Translational models must be developed and tested for delivering genomic information to public health practitioners, health care providers, and the public. It is necessary to learn how to tailor information and change behavior based on genetic information and to identify who is at risk, how to change risk, and how to target populations.
Additionally, current heuristic methods are no longer adequate to the task. Informatic support is needed for the clinician and public health practitioners who cannot draw upon a base of experience. In order to create the body of information, there must be databases that allow clinical experience to be captured and aggregated for new, more finely grained categories used for risk assessment, for example, analyzing what is genetic and what is environment, recognizing that both types of risk may present opportunities for intervention. For example, a child with PKU, a disorder that clearly results from genetic variation, is treated with a low phenylalanine diet, an environmental intervention, not gene transfer.
Educational needs in the area of public health genomics must be determined. What do clinicians need to know? What about public health researchers and practitioners? What do individuals in various risk categories need to know? Who needs to be educated about what and why? Effective mass media public education programs must be developed that
recognize the importance of language and negative attitudes. Effective public education requires
Clear, specific objectives
Adequate exposure in a consistent way
Behavioral research that incorporates the complexities of what we know about behavior change and the use of genetic information.
The best genomic information should be made available to the population to obtain the maximum population benefits in an equitable way. Mechanisms are needed to ensure that genetic information is used to reduce health disparities. Furthermore, it is important to determine what the legal system can do in terms of protecting against injustice and avoiding discrimination.
There are many lessons to be learned from existing large-scale database projects (biobanks). An important conclusion is that there needs to be more harmonization among these databases. Biobanks are a global public good, but there is a need for harmonization of systems, provision of safeguards that serve the public good but protect the community, and assurance that biobanks are organized, systematized, and searchable. Guidelines and tools for harmonization should be developed and should address the following questions:
What is harmonization?
What should biobanks look like?
How should one provide adequate safeguards that facilitate operations but protect as necessary?
Finally there is the issue of the targeted use of drugs (pharmacogenomics). Such targeted use could facilitate analysis of current underuse, overuse, and misuse of drugs. Targeted and perhaps more limited use of drugs suggests new possibilities for cost savings and avoidance of drug–drug interactions and adverse drug reactions. It also raises the problem of generating adequate revenue to invest in expensive development of pharmacologic agents that are targeted at small populations.
In conclusion, the committee agreed with many of the speakers who pointed out that genomics holds the promise of providing great benefits for population health, yet also carries the shadow of vastly increasing health disparities if segments of the population are not able to access genomic technologies and services. As Dr. William Foege said, “The chal-
lenge to public health genomics is to overcome inequitable allocation of benefits, the tragedy that would befall us if we made the promise of genetics only for those who could afford it and not for all of society. Social evolution as a result of genomics will be what we want it to be, and now is the time to make our case.”