Office of Public Health Genomics
2006 Program Review Book
Integrating Genomics into Public Health Investigations: CDC Influenza Public Health Genomics Initiative
The CDC Influenza Public Health Genomics Initiative is a model project to demonstrate integration of human genomics into public health investigations.
With the ongoing threat of seasonal influenza and the potential emergence of new, more virulent strains of influenza, CDC and its partners are developing an initiative to investigate the role of population genetic variation in the epidemiology of influenza morbidity and mortality and the effectiveness of public health interventions (e.g., vaccination).
Improve influenza preparedness by advancing studies of human genetic variation in relation to influenza infection.
Anticipated Products and Public Health Impact
- Protocols for acquiring DNA and other biologic samples in the epidemic setting, including appropriate methods for obtaining informed consent and for sample transport, preparation and storage. An “off-the-shelf” protocol will be available for immediate use in epidemic settings.
- OPHG has contracted with America’s Health Insurance Plans (AHIP) to develop a multi-site DNA bank from patients within group health plans that can be used to study the role of genetic factors in influenza disease severity and vaccine effectiveness and side effects response to therapy.
- OPHG will host a workshop January 11-12, 2007 to develop priorities for public health genomics research in influenza, focusing on the epidemic and managed care settings.
Beyond Gene Discovery (BGD) Initiative: Developing a National Genomic Profile for the U.S. Population
In collaboration with public, private and academic partners, CDC will assess population genetic variation in the U.S. in relation to health and disease and develop strategies for using genetic information to impact health and eliminate disparities among population groups. The NHANES provides the unique national resource for investigating the effects of genetic variation on health and will serve as the initial focus of BGD. Genetic samples are available for nationally representative probability samples of approximately 15,000 persons enrolled in two NHANES. The survey oversamples the two largest race/ethnic minority groups, non-Hispanic blacks and Mexican Americans, along with other subgroups of the population. Information on multiple aspects of health obtained through interview, laboratory tests and direct examinations is also available for the NHANES participants. BGD marks the first large-scale effort in the U.S. to coordinate the comprehensive identification of the associations among variations in genotype, phenotype, and risk factors in a representative sample of the population, laying the groundwork for understanding the relation between human genome variation and health status.
BGD will offer an opportunity for an unprecedented look at interactions among numerous genetic variants, environmental exposures and behavioral factors contained in the clinical, biochemical, and metabolic profiles of a large number of people of all ages. This research will enhance the value of many ongoing gene discovery studies, helping to translate findings into new targets for prevention, diagnosis, and treatment of common diseases. By measuring the population prevalence of key genetic variants, BGD will provide the basis for estimating the numbers of people who may benefit from particular genotype-based screening or diagnostic tests, drugs, or other preventive or therapeutic interventions. BGD represents the whole U.S. population, including minority racial/ethnic groups. By taking an inclusive, evidence-based approach to personalized medicine, BGD can help address disparities with data instead of oversimplification.
Applying Genomic Applications to Population Health
A new team is being formed in NOPGH to develop and evaluate genomic applications that use clinical and genomic information such as familial risk assessment, signs and symptoms recognition, and genetic testing to promote the prevention and early detection of both traditional genetic disorders and common chronic diseases. For many years, integration of genomic applications into clinical practice has been focused on genetic testing for individually rare single gene disorders. More recently, we are seeing the introduction of genomic applications for common chronic diseases such as using genetic markers in early identification of cancer or targeting therapies based on genotype that optimize response and avoid adverse drug reactions. With the completion of the human genome sequence, we can expect in the coming years the increasingly rapid development of new genetic tests – including concurrent testing of multiple genetic markers using microarray technologies (i.e., multiplex testing) – that will be used to help refine diagnoses, improve risk prediction, and target therapies for both traditional genetic disorders as well as common chronic diseases. In the meantime, there are already genomic applications being used to some extent in clinical medicine which could be applied at the population level to assess disease risk, influence early disease detection, and provide guidance for disease prevention or management. These applications, including familial risk assessment, signs and symptoms recognition, and genetic testing, when used as public health strategies, could lead to overall population health benefits.
Family history is an important tool for identifying individuals and families with genetic susceptibility to common chronic diseases such as coronary heart disease, stroke, diabetes and most cancers, as well as the rare single gene disorders like cystic fibrosis, sickle cell anemia, hereditary forms of breast and colorectal cancer, and hemochromatosis. As an integral part of primary care and preventive medicine, familial risk assessment has the potential to identify individuals at risk of disease, those with subclinical disease, and those who may already be affected but are undiagnosed.
There are many single gene disorders across the life span that could benefit from early disease detection and interventions through a closer partnership between medicine and public health. Many affected persons with genetic diseases such as hereditary hemochromatosis (HH), familial hypercholesterolemia (FH), and primary immune deficiency disorders, for example, are either missed by the healthcare system or not diagnosed early enough for effective and appropriate interventions to work. Thus valuable opportunities for disease and disability prevention are lost. A public health approach employing public and provider education about symptom recognition, surveillance strategies, screening, and referral to appropriate services, could be used to enhance existing health care practice leading to earlier diagnosis of these disorders.
While efforts are underway to examine the validity and utility of genetic tests that are being transitioned from research to clinical and public health practice, there is little being done to examine the uptake of specific tests and the outcomes of genetic testing services. There is a need for genetic testing surveillance and applied research in primary care to monitor the integration and penetration of genetic testing into the healthcare delivery system. Genetic tests for more than 1,200 diseases have been developed, with more than 1,000 currently available for clinical testing. Most are used for diagnosis of rare genetic diseases, but a growing number have population-based applications, including carrier identification, predictive testing for inherited risk for common diseases, and pharmacogenetic testing for variation in drug response. These tests and other anticipated applications of genomic technologies for screening and prevention have the potential for broad public health impact.
The OPHG team will work with CDC collaborators and external partners to identify the genomic applications and diseases that are ready and most appropriate for a public health approach. Activities for the team might include:
- Developing an internal CDC working group to define the scope and the plan for the team’s activities.
- Seeking appropriate partnerships and input from outside CDC.
- Assembling background information on diseases that could potentially benefit from genomic applications, including familial risk assessment, signs and symptoms recognition, and genetic testing.
- Identifying gaps in knowledge and research needs for implementing these genomic applications in clinical practice and public health.
- Developing a research and evaluation agenda and sponsoring demonstration projects that can show the population health benefits of genomic applications.
- Establishing a network of research centers that might include academia, states, professional organizations, and other agencies.