Ph.D. Core Knowledge Areas

Two core knowledge areas are central to the study of public health genetics at the doctoral level:

  1. Genomics in Public Health (genetic epidemiology, and ecogenetics and pharmacogenetics)
  2. Implications of Genetics for Society (ethics and social science, law and policy, and health economics and outcomes research)

Ph.D. students acquire a basic competence in both core knowledge areas. Each student's dissertation topic falls broadly within one of the core knowledge areas, and the student is expected to develop additional expertise in that area through electives and thesis work.

The overall content of each area is described below.

Core Knowledge Area A: Genomics in Public Health

Genetic epidemiology is a rapidly evolving field that focuses on complex diseases (those usually not caused by a single gene) in which both genetic and environmental factors contribute to the disease etiology. Genetic epidemiology incorporates human genetics, epidemiology, biostatistics, statistical genetics, bioinformatics, and molecular biotechnology into studies designed to identify genetic and environmental influences on diseases among relatives and in diverse human populations.

Research in genetic epidemiology. Research methods in genetic epidemiology include studies of twins and extended families, heritability and segregation analyses, genetic mapping studies using genetic linkage analysis, and population-based genetic association studies. Research in genetic epidemiology will lead to better prediction of disease among high-risk individuals and families, as well as more effective environmental and behavioral interventions to prevent disease.

With Whole Genome Sequencing (WGS) and 1000 Genomes Project highlighting the genetic diversity inherent in populations, genetic epidemiology has become an essential discipline for evaluating genetic influences on disease. Genetic epidemiology also holds much promise for identifying gene-gene and gene-environment interactions that contribute to health outcomes.

Genetic basis of adverse reactions. Some people respond adversely to doses of certain chemicals that most people tolerate well. Such adverse reactions, sometimes called idiosyncratic reactions, often have a genetic basis. In many instances, the increased sensitivity to the pharmacological or toxicological effects of the chemical is caused by a genetically determined variation in the way the chemical is metabolized (biotransformed) in the body. The recent development of rapid DNA sequencing and high-throughput genotyping in populations has made it possible to identify hundreds of specific genetic polymorphisms in a plethora of different drug-metabolizing enzymes that may impart differential sensitivity to a great many drugs and chemicals found in our environment.

In addition, genetic variation in cellular receptors, signal transduction pathways, DNA repair, cell cycle regulators, and other biochemical pathways that are targets of drugs and other chemicals, both exogenous and endogenous, are continually being discovered. Genetically determined differences in the structure of protein targets, or in their cellular concentration, can affect the intrinsic pharmacological response to a given level of drug/chemical exposure.

The closely related fields of ecogenetics, pharmacogenomics, and toxicogenomics address how specific genetic differences in an individual confer increased or decreased response to drugs and other chemicals. Appreciating these differences can lead to a better understanding of (a) adverse drug reactions, (b) failure of certain drug therapies, (c) new molecular targets for prevention, diagnosis, and treatment of diseases, and (d) the etiology of environmentally related diseases. Such information will greatly enhance the development of effective prevention strategies and improve the diagnosis and treatment of diseases that represent public health issues.

Core Knowledge Area B: Implications of Genetics for Society

The recent completion of the human genome sequence has drawn attention to the implications of genetic science and technologies on individuals and society. Technologies are emerging that can create individual genetic profiles embedded in a microchip on a gene chip. Healthcare providers might utilize this genetic profile to identify risk for certain diseases well in advance of their development or identify genetic changes to facilitate diagnosis in early stages of a disease.

The genetic profile might also be used to find the right drug and dosage to ensure optimum treatment with minimum adverse effects. Drug companies are likely to take advantage of this technology to develop new, safer, and more specific drugs for the treatment or even prevention of diseases.

Pluses and minuses. The technology thus appears to promise extraordinary medical benefits. However, it also poses potential harms. Information about future disease risks could stigmatize individuals or cause psychological distress, with the effect that the diagnosis is more harmful than the disease. Certainly some diseases carry the risk for stigmatization; for example, a future risk of dementia could have more profound social consequences than a future risk of heart disease. Similarly, the social consequences of genetic information are likely to vary from one culture to another.

Policy implications. Genetic information will typically predict a probability of future disease, not a certainty, and policies will be needed to determine what level of risk constitutes information of public health significance. Such policies could have major social, economic, and legal consequences, affecting, for example, whether a person with a susceptibility to an environmental exposure could be barred from certain workplaces, or whether healthcare providers have a duty to disclose genetic risks to family members who are not their patients.

A major challenge will be to develop strategies for defining and studying the potential social risks of genetic information so that the scope of the risks can be defined and preventive measures assessed and implemented. To develop such strategies will require the application of social and ethical theories as they interact with law and policy.

Stakeholders and decision-makers. Genetic technologies are developed in the academic sector and the marketplace, applied in the healthcare delivery system, paid for by patients and health insurers, and regulated by federal, state, and local governments. Decision-makers in each of these segments influence how these technologies are used and what their ultimate influence on public health will be.

There are many stakeholders with an interest in public health genetics, each with a particular set of objectives and point of view. Stakeholders are often in conflict over the interpretation of scientific data, the importance of privacy and confidentiality, the appropriate use of genetic technology, and access to genetic services. The goal of public policy is to balance the interests of public and private stakeholders in these areas so as to maximize the welfare of those affected.

Inevitably, policy choices will involve tradeoffs between efficiency and equity considerations. Policy-makers must consider historical precedents and the cultural context in which a policy will be applied. As a new technology, genetics may challenge longstanding assumptions and raise new questions for policy-makers.

As the knowledge of genetic contributors to disease increases, policy-makers will be challenged to devise strategies that strike a balance between the potential benefits of genetic technology and potential harms, including the
potential for discrimination and stigmatization based on genetic identity.