Genomics for Public Health Practitioners
Genetics vs. Genomics
The Human Genome Project
Applications page 2
Public health genomics
What is hype?
What is reality for public health?
Top 10 causes of death in the U.S.
Gene-environment spectrum of disease causation
Genetic susceptibility not equal to health destiny
Potential Interventions page 2
Potential Interventions page 3
We should wait?
What we should do now
What we should do now page 2
Genomics in action
Pedigrees page 2
Health Family Tree
Health Family Tree Project
Health Family Tree Project page 2
Health Family Tree Project page 3
Health Family Tree Project page 4
CDC Family History Public Health Initiative
How can we learn more?
How can we learn more? Page 2
How can we learn more? Page 3
(Music intro for Genomics for Public Health Practitioners…)
Thank you for your interest in Genomics for Public Health Practitioners: The practical application of genomics in public health practice. This 45 minute introductory presentation on genomics in public health is intended for public health practitioners who have minimal experience in the area of genomics as it pertains to public health. Genomics for Public Health Practitioners was developed through a collaborative effort between three Centers for Genomics and Public Health and the CDC Office of Public Health Genomics.
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Today we will explore the growing impact of the genomic revolution on public health practice in the new millennium. We will address the following issues:
- 1st we’ll review important terminology that will be useful for understanding how genomics relates to public health,
- 2nd we’ll discuss and attempt to clarify some misperceptions that we have heard previously about genomics and public health,
- 3rd we’ll present an example of how genomics has been and could be incorporated into public health programs,
- And last we will address how you can learn more about the utilization of genomics in public health.
Many people associate the term genetics, the study of single genes, with classic Mendelian principals of inheritance in which one gene represents one phenotype or trait. Today’s scientists are using powerful new tools for sequencing DNA and all the genetic material of entire organisms - or their genomes - including humans. These advances will improve our understanding of how multiple genes and gene products interact with other genes and environmental factors. We use the term genomics here to denote this more complex model of health and disease.
So, for our purposes, genetics is defined as the study of single genes and their effects, where as genomics is the study of the functions and interactions of all the genetic material in the genome - including interactions with environmental factors.
Knowledge of the human genome is increasing because of the Human Genome Project. The project is an ambitious collaborative effort to understand the genetic code of life. The goals of the project include:
- Sequence the three billion base pairs DNA of entire genome, in fact this goal was completed in 1983
- Identify the thirty thousand genes in the human genome
- Create databases and tools for data analysis and DNA sequencing
- And address the ethical, legal, and social issues as they arrive
Progress on these goals has been rapid and new information is accumulating daily.
Because of the Human Genome Project, it is predicted that genomics will revolutionize medicine. But “How will genomics affect public health? What is public health genomics?”
For our purposes, we define public health genomics as the study and application of knowledge about all the elements of the human genome and their functions, including their interactions with their environment, in relation to health and disease in populations.
Public health genomics encompasses a variety of activities, some of which include the following:
- Conducting surveillance of diseases or conditions with a known genetic component, such as birth defects. Surveillance efforts are expanding to include cancers with a genetic component and other more common disorders.
- Performing epidemiological studies that allow researchers to examine gene-gene and gene-environment interactions to better aid in the identification of genetic risk factors for common, complex diseases such as cardiovascular disease, asthma, and diabetes.
Public health genomics also includes:
- Developing programs and policies, such as population-based screening recommendations
- Educating health care providers and the public about genomics. This might include public health campaigns, increased awareness through seminars or other educational channels, or presentations such as this one.
- Assuring the availability of and access to genetic services such as genetic testing and medical evaluation for genetic conditions
- Evaluating genetic tests and services. This includes examining the analytic validity, clinical validity and clinical utility of genetic tests.
Analytic validity – The analytic validity of a genetic test defines its ability to accurately and reliably measure the genotype of interest (taken from ACCE: A CDC-Sponsored Project carried out by the Foundation for Blood Research)
Clinical validity – The clinical validity of a genetic test defines its ability to detect or predict the associated disorder (phenotype) (taken from ACCE: A CDC-Sponsored Project carried out by the Foundation for Blood Research)
Clinical utility – The clinical utility of a genetic test defines the elements that need to be considered when evaluating the risks and benefits associated with its introduction into routine practice (taken from ACCE: A CDC-Sponsored Project carried out by the Foundation for Blood Research)
As a result of predictions that the human genome project will revolutionize medicine, a number of misperceptions have been generated regarding the role of genomics in medicine and public health. Here are some common misperceptions:
- The role of genomics and revolutionizing medicine and public health is all hype.
- Genomics is not relevant to me or the area of public health in which I work
- We are our genes. In other words, genetic susceptibility equals health destiny - and if we can’t change our genetic make-up genomic information isn’t useful in public health.
- Along those same lines, some believe there are no risk-reducing interventions based on genomic information.
- And lastly some think we should wait to learn more about genomics until we learn more about the role genetics plays in disease. The science is just not ready.
Let’s take a moment to discuss and hopefully clarify some of these misperceptions.
To address the first misperception, that the role of genomics in revolutionizing medicine in public health is all hype. Let’s first acknowledge that “yes” there has been a lot of hype. Some of it is demonstrated in some of these dramatic magazine covers (Time, Popular Science, Newsweek). You have probably seen or heard some of these sensationalized views of genomics.
There are even private companies that now offer personalized genetic testing that is advertised in Web sites and retail stores. Some promise to inform individuals of their risk of heart disease and osteoporosis, while others promise to provide advice about nutritional supplementation or foods to achieve a higher level of overall health based on an individual’s make-up.
So, with so much hype out there, what is reality?
- First, the reality is that genetics has been successfully incorporated into public health for decades - through state newborn screening programs - so genetics is relevant to public health and it can be used in public health practice.
- Second, reality is that there has been a lot learned through the human genome project, and research stemming from it. But there is still a lot more to be learned. For example, research studies have been useful in identifying genetic risk factors for disease susceptibility. However, more population-based data about genes and diseases is needed to quantify the impact of genetic and environmental factors on disease risk.
- So, public health practice needs to build upon and enhance the existing public health infrastructure in order to begin identifying opportunities to apply genomic advances to public health practice.
The second common misperception many people have is that genomics isn’t relevant to their area of work. Listed here are the top 10 leading causes of death in the U.S. in the year 2000. (heart disease, cancer, cerebrovascular disease, chronic lower respiratory disease, accidents/unintentional injuries, diabetes, pneumonia/influenza, Alzheimer’s disease, kidney disease, septicemia.) Nine of these 10 have a genetic component. From this list, you can appreciate the relevance of genomics to the broad spectrum of genetic diseases of public health importance. (Reference: National Vital Statistics Report, Vol 50, No. 16, September 16, 2002.)
The next misperception to clarify is that “we are our genes” or that we are destined to develop a disease or exhibit a behavior if it is in our genetic code. It is true that there are some diseases caused solely by mutations in certain genes, such as Huntington’s Disease. It is also true that some outcomes such as unintentional injuries are caused predominantly by environmental factors. However, most of the common chronic diseases that affect the majority of the population -- such as Diabetes, cancer, asthma, and heart disease, are actually caused by a combination of predisposing genetic and environmental factors, and lie somewhere in the middle of a gene-environment spectrum of disease causation.
And while it is true that our genes cannot be modified, we do have some control over our risk for developing disease. We can modify our behavior and our environment.
The bottom line is that genomics may not substantially change the primary goals of health promotion and disease prevention. But it may make interventions more effective by allowing genetic, behavioral, and environmental factors to be addressed. So genetic susceptibility, the risk for developing disease based on genetic make-up, is not health destiny!
Along those same lines, another misperception is that we have no interventions. While it is true that we can’t change our genetic make-up, there are many lifestyle and medical interventions that if adopted may modify the risk of developing or allow the early identification of disease. Recognizing the role of genetic susceptibility in common disease may allow modification of public health recommendation for some populations. An individual might modify screening and/or medical monitoring based upon family history information which reflects the consequences of genetic susceptibilities combined with shared environmental factors.
For example, in cases where there is a family history of colon cancer,
- screening recommendations might be modified to begin screening earlier than the general recommendation of age 50,
- engage in more frequent screening, or both.
- in incidences where the family history of colon cancer susceptibility suggests a dominant pattern of inheritance, or if there is a strong family history of other cancers in the family, a referral for cancer risk evaluation and counseling about genetic testing for specific cancer susceptibility genes, might be useful.
By including what we know about genetic susceptibilities within public health messages, we make a population message more personalized and can influence the recommendations made for that individual.
Interventions could also focus on modifying exposures to environmental factors that may interact with known genetic susceptibilities.
For example, we know the specific enzymes in the metabolic pathways that detoxify environmental chemicals, such as pesticides, may have different levels of activity due to small variations in the genes that code for them. For instance, there are multiple genetic variants of peraoxonase, an enzyme involved in the metabolism of certain pesticides. People with certain variants of this gene have lower levels of enzyme activity and cannot metabolize these agents as quickly as those without the variant.
These people can experience symptoms of pesticide toxicity if exposed to pesticide levels that are considered to be within accepted exposure levels. One intervention might be to screen individuals with significant exposure to pesticides for genetic variants of peraoxonase. Another might be to reconsider allowable levels of pesticide exposure to ensure they are safe for all workers.
Genetic susceptibility information might also have the potential to make public health interventions that promote positive health behavior changes more effective such as:
- adopting a healthier diet,
- engaging in exercise,
- kicking a smoking habit,
- or abstaining from alcohol.
For instance, knowledge about increased genetic susceptibility for a certain disease in the population could allow public health professionals to stratify individuals into risk categories, based upon genetic susceptibility information, and then to specifically target public health messages or behavioral interventions to those at high risk.
At an individual level it might be possible that public health interventions based upon genetic susceptibility information, may be more effective because of the personal nature of such information. For instance, consider a person who has had several family members develop heart disease at an early age. Perhaps having some understanding of the connection between this family history and the individual’s risk of heart disease might increase his or her motivation to adopt healthier behaviors, such as diet modification and increased physical activity. This is the type of issue that applied public health research can and needs to address.
The last misperception to clarify is that we should wait until we know more. The human genome has been sequenced. Laboratories are already testing for over 1,000 genetic conditions. In the summer of 2003, a biotechnology company began a consumer marketing campaign for breast and ovarian cancer susceptibility testing. This is the first time an established genetic test has been marketed directly to the public, and this campaign is likely to be a prototype for direct-to-consumer marketing of genetic tests in the future. We can’t wait. The public health community needs to be prepared to respond to issues raised by the rapid and sometimes premature marketing and introduction of genetic tests to the medical community and the general public. We also need to be able to identify appropriate opportunities for incorporating genomics into public health interventions.
So, if it is not too soon to incorporate genomics into public health practice, what can we, as public health professionals, do? There are several things we can and should do right now to promote this integration, including the following:
- Educate ourselves and our constituencies on how genomics can be used to address public health problems. For example, public health program staff need to understand the genetic basis of common chronic diseases and to monitor the evolving research in this area, in order to incorporate genomics into existing public health programs. Additionally, public health professionals can play a role in educating the public about genomics. Public health educational channels can also serve as a resource for non-biased information about genetic tests.
- Utilize existing data sources to help determine the genetic contributions to disease. Such data sources might include death records and surveillance data. Conclusions drawn from these data could ultimately enable the planning of more cost effective programs and services.
- Identify population at high and moderate risk who could benefit most from medical, behavioral and environmental interventions.
In order to quantify the population-wide burden of disease that is attributable to various risk factors, we should take into consideration risk factors that are alterable, such as behavior and diet, as well as those which are not, such as age and genotype.
Public health should also play a role in supporting the development and enactment of sound policies regarding advancing genetic technologies with particular considerations of associated ethical, legal, and social issues. Guidance is especially needed for issues such as safe and effective use of genetic tests, and technologies and the appropriate use of genetic information by insurers and employers. Public health can play an important role in educating both policy makers and the public about these issues, and how current laws and regulations address them. Public health can also play a role in convening a broad spectrum of individuals necessary for developing sound policies in this area.
And lastly, public health should develop and enhance partnerships to address the many issues arising out of this post-genomic era and guide public health activities. Relevant stakeholders might include researchers, medical practitioners, behavioral scientists, health promotion experts , health care providers and payers, policy makers, and of course, the general public. These stakeholders should be advised on the broad spectrum of activities undertaken by public health - from policy development to program planning and evaluation.
While there is much that public health can and should do to start integrating genomics into public health practice, we cannot ignore certain challenges. These challenges further emphasize the need for leadership in all areas of public health. Some of the challenges include:
- Lack of population data –Population data are needed to quantify the impact of gene variants and modifiable factors interacting with these gene variants on the risk of disease, death, and disability.
- Rapid commercialization of genetic tests – A test often becomes available to the public before the analytic validity, clinical validity, and clinical utility are known; before a treatment or intervention for a disease is available; before guidance is available to health care providers on appropriate use and practice; or before associated ethical, legal, and social implications of its use are considered.
- Ensuring quality of laboratory testing- There is a need to address concerns related to laboratory quality issues, such as standardization and validation of testing methods, quality assurance and proficiency testing, personnel qualifications, and test ordering and result reporting.
- Availability of and access to interventions – Medical and public health interventions may be limited for many diseases.
- Potential discrimination against and stigmatization of individuals and groups - These could include societal discrimination, employer discrimination, and insurance discrimination.
- Public and professional education – As advances in genomics begin to be incorporated into every level of public health, it will be important for the public health workforce to understand basic genomic concepts and how they apply to everyday practice. It will also be necessary to effectively convey appropriate information about genomics to the public.
We have talked about what genomics is and what the misperceptions are. We have addressed the hype that surrounds the headlines in the popular press and how this leads to unrealistic expectations and perceptions of genetic destiny. So, are there ways that genomics has been used within a public health context to improve the public’s health? Yes, there are! Two public health programs that use biological family history as a way to identify individuals and families at increased risk of disease are the Utah Health Family Tree Study and the CDC Family History Public Health Initiative.
Now, you might be thinking, Why family history? And how could this be genomic information? Family history reflects the influence of factors that are shared between family members. This includes environmental as well as genetic factors. A family history tool collects genomic information because it collects information about medical conditions present in a family, and also tracks the relationships between family members. Family history tools can also document behaviors and conditions that are associated with poor health outcomes, such as obesity, diet, smoking and exercise habits. It can also document common environmental factors that are associated with both desired and undesired health outcomes. Finally, it can collect information on social situations and cultural mores that may impact health.
The family history can be documented in several ways, but the gold standard is the pedigree. A pedigree documents all types of information in a graphic format that can be continually updated as new information becomes available and it is easy to read and analyze for relationships and patterns of traits within families.
Here is an example of a pedigree. The circles are females, and the squares are males. A line drawn directly between a circle and a square is a marriage or mating line. A sibship line connects the offspring of this union, indicating that they have the same parents. The children are listed from left to right from oldest to youngest. As you can see, there are four siblings. The eldest are twin females, followed by a male and female respectively.
We have already touched on the many advantages of a pedigree format for collecting large amounts of information. But, is the pedigree appropriate for the public health setting? Sometimes yes, sometimes no. The pedigree, for all its power and flexibility, has some features that may be disadvantageous in specific situations. First of all, it requires some skill and practice for effective use. Also, it is very time consuming to administer. A detailed pedigree on the average family can take 20 or 30 minutes, which may be impractical and expensive. Also, the data collected in a pedigree format may be difficult to code in formats that are easily analyzable. Finally, the information that is collected must be a true reflection of the health conditions in the family.
One attempt to use family history in a public health setting is the Utah Health Family Tree Study. This study attempted to adapt the pedigree format into a tool to identify families at risk for later onset chronic diseases. After determining its sensitivity and specificity for this purpose, the goal was to use the information collected for personalized public health interventions aimed at preventing disease.
This is what the Health Family Tree looks like and what information was collected on each family member. As you can see, the tree is really a pedigree, in which you can readily see the relationships of the family members. The same information is collected on each family member and is limited to chronic diseases and their associated risk factors. These chronic diseases have a multifactorial etiology, meaning both genetic susceptibility and environmental factors may influence incidence and severity of disease. By collecting the information in this type of format, the power of the pedigree can be preserved while some of the disadvantages can be alleviated. The data is easy to code and is collected by the family members themselves. The information can be analyzed to identify patterns of chronic disease or risk factors within families and to identify families at an increased risk for chronic disease. Based on this information, appropriate interventions can be implemented and have been shown to have positive effects on reducing risk factors and improving healthy behaviors.
Over the last twenty years, the Health Family Tree has been used in various forms and at various times in Utah, Texas, Massachusetts, Minnesota and North Carolina and many of these experiences have been published in the literature. To date, at least one hundred thirty thousand families have participated in this process and have contributed their family history data for analysis.
In Utah, the complete program was a partnership between the University of Utah, state and local public health, and public high school students. The Utah Department of Health and the University of Utah cardiovascular genetics program developed a curriculum aimed at the high school level. In Utah, this was implemented in 10th grade health classes. Since the project involved collecting health information, parental consent was required, and parents could consent to several levels of participation. Full participation included mailing of results back to the student's home and permission to be contacted. For more detailed information on how the study was performed, refer to the reference indicated here. Briefly, after participating in the classroom module, the students were sent home with a family health tree to fill in the information on the health and risk factors for themselves and their relatives. The family information was inserted into a mathematical algorithm to calculate a family risk score. Families identified as being at high risk for developing a chronic disease were offered a public health intervention.
Although several chronic diseases with a genetic component are included in the Health Family Tree, the majority of the data that has been published is related to coronary heart disease. The data presented here is from a 2001 article in the American Journal of Cardiology. This data is based on the analysis of the family history data from one hundred twenty two thousand Utah families. Fourteen percent of these families had a positive family history of coronary heart disease, which accounted for over seventy percent of the cases of early coronary heart disease in this population. In addition, these families accounted for about half of the coronary heart disease observed in the population overall.
When a similar process was applied to a family history of stroke and stroke risk factors, the results were perhaps even more striking. Eleven percent of families accounted for eighty six percent of all strokes within the population.
The cost of this screening is low. In this study, it cost only twenty seven dollars to identify each high-risk family, not including any of the costs for interventions. This compares favorably with the cost of other screening tests.
A process that can identify high-risk families is only useful if there are effective and acceptable interventions that can reduce risk and improve health. Most data that has been collected or published has been primarily focused on the ability to identify at-risk families, but there is at least one report describing the intervention process used in Utah. This study looked at a population of 16,000 families that were screened with the Utah Health Family Tree. In these families, about 10% were determined to have a strong, positive family history for a preventable condition and were contacted with these results and offered a personalized public health intervention.
Of the high risk families, 95% were contacted by a community health nurse and 65% of these received one in-home visit for counseling and referral. The interventions utilized were based on standard of care protocols for prevention or treatment of specific conditions. The interventions emphasized strategies to reduce risk, such as counseling on lifestyle and behavior change, and referral for primary or specialty care and additional screening, as appropriate. These families were followed annually with a questionnaire to track intervention effectiveness over time, and as a mechanism to reinforce health behaviors for several years. An equal number of families were determined to be at the population risk for developing chronic disease and were also followed annually with the same questionnaire, but did not receive any other intervention.
Some of the data collected from these surveys are presented in this slide. Families that were identified as being at high risk for developing a chronic disease were scored on several behaviors that are correlated with the prevention or early diagnosis of chronic disease. These families were compared with control families that had family risk scores in the average range. Over the four years that data were collected, there was an improvement in health behaviors in both groups, but the most marked improvement was in the high-risk family group. For example, at the time when they first came to attention due to screening, only thirty five percent of families had an annual medical exam, compared to seventy five percent of control families. After four years of annual follow up, almost ninety percent of both high risk and control families were having an annual medical checkup. The data are also striking for parameters related to regular monitoring of blood pressure levels, weight loss, exercise and healthy diet.
Another initiative to develop a family history tool for identifying apparently healthy people who may be at increased risk for a number of common diseases began in early 2002 by the CDC Office of Public Health Genomics in collaboration with several CDC programs, NIH institutes, universities, professional organizations, and health departments. The goal is to evaluate the use of family history for assessing risk of common diseases and influencing early detection and prevention strategies. Major phases of this initiative include: 1) assessment of existing strategies to use family history for disease prevention, 2) development of a new tool for public health and preventive medicine called Family Healthware, 3) pilot testing and evaluation of the tool, and 4) development and implementation of public health campaigns and provider education.
More detail on this initiative can be found at the listed website. http://www.cdc.gov/genomics/famhistory/index.htm
We hope that we have demonstrated the growing impact and promise of the genomics revolution on public health practice in the new millennium. We’d like to leave you with a few take home messages:
First, that genomics holds promise for public health.
Second, it is relevant to most public health professionals.
Third, genetic susceptibility is not health destiny.
Fourth, there are options for reducing risk of diseases with a genetic component.
Finally, genomics is being incorporated into public health practice.
So now that you have an introduction to genomics and public health, where do you turn next for more information? This presentation is meant to be an introduction to a larger educational resource called Six Weeks to Genomics Awareness. Six Weeks to Genomics Awareness was developed as part of a collaborative agreement with the CDC under the lead of the Center for Genomics and Public Health at the University of Michigan with assistance from two other Centers for Genomics and Public Health, at the University of North Carolina, and at the University of Washington. It includes six modules on genomics and public health.
The six modules include:
- The Human Genome & Heredity
- Genes in Populations
- Genetic Testing
- Gene-Environment Interactions
- Ethical, Legal, and Social Issues Associated with Genomic Applications
- Genomic Resources at the State & National Level
To learn more about Six Weeks to Genomics Awareness, including how you can participate in the series, contact one of the Centers for Genomics and Public Health
Information regarding the Centers for Genomics and Public Health can be found at the listed websites.
- University of Michigan http://www.sph.umich.edu/genomics/
- University of North Carolina (no longer available)
- University of Washington http://depts.washington.edu/cgph/
More information regarding other resources about genomics in public health can be found at these websites, including the CDC Office of Public Health Genomics.
- National Newborn Screening and Genetics Resource Center http://genes-r-us.uthscsa.edu/
- Genomics: A Guide to Public Health http://www.astho.org/Display/AssetDisplay.aspx?id=5091
- CDC Office of Public Health Genomics http://www.cdc.gov/genomics
We would like to thank you for taking the time to view this introduction to the practical application of genomics in public health practice. We hope today’s presentation will encourage you to consider the relevance of genomics in your area of public health, and encourage you to contact us with any comments or suggestions.