tions, and evaluate the effectiveness of health programs and services in improving the population's health (28).
Over the last two decades, epidemiologic methods and approaches have been increasingly integrated with those of genetics through the discipline of genetic epidemiology, which seeks to identify the role of genetic factors in disease occurrence in populations and families (29). In addition, a new brand of epidemiology has emerged-molecular epidemiology-that seeks to study disease occurrence using biological markers of exposure, susceptibility and effects (30).
Most discoveries for gene variants are based on studies of high-risk families or selected groups. To translate the results of this genetic research into opportunities for treating and preventing disease and promoting health, population-based epidemiologic studies are increasingly needed to quantify the impact of gene variants on the risk of disease, death and disability, and to identify and quantify the impact of modifiable risk factors that interact with gene variants. The results of such studies will help health professionals to better target medical, behavioral and environmental interventions. Epidemiologic studies are also required for clinical validation of new genetic tests, monitoring a population's use of genetic tests, and determining the safety, effectiveness and impact of genetic tests and services in different populations.
To accomplish translation of genetic discoveries into public health practice, epidemiologists must collaborate with practitioners of other disciplines such as clinical genetics, laboratory sciences, behavioral and social sciences, communication sciences, ethics, and law. A combined genetic-epidemiologic approach is essential for better understanding disease etiology and developing molecular diagnostics. Data generated from such collaborations are urgently needed in developing medical and public health policy. For example, issues have been debated regarding population-based genetic testing for breast cancer in relation to BRCA1 (31); Alzheimer's disease in relation to the Apolipoprotein E-E4 allele (32); and iron overload in relation to the hemochromatosis gene (33). Given the paucity of population-based epidemiologic data regarding the frequency of and disease risks and environmental interactions for many newly discovered human gene variants, there is concern that appropriate health policy on the use of genetic tests may not be possible.
Human Genome Epidemiology
The term "human genome epidemiology" (HuGE) denotes an evolving field of inquiry that systematically applies epidemiologic methods and approaches in population-based studies of the impact of human genetic variation on health and disease. HuGE can be viewed as the intersection between genetic epidemiology and molecular epidemiology (34). Whereas genetic epidemiology has traditionally focused on techniques to find disease genes using linkage and segregation analysis, and molecular epidemiology focuses on using biological markers in epidemiologic studies.
The wide spectrum of topics addressed by investigators working on human genome epidemiology and selected examples are shown in Table 4(36). The spectrum ranges from population-based epidemiologic research on gene variants to evaluation of genetic tests and services. Ultimately, HuGE represents the application of clinical and molecular research to a population setting and involves the collaboration and contribution of numerous specialties.
In 1998, a collaboration of individuals and organizations launched the Human Genome Epidemiology Network (HuGE Net). This global effort seeks to (1) promote collaboration in developing and disseminating of peer-reviewed epidemiologic information on human genes; (2) develop an updated and accessible knowledge base on the World Wide Web; and (3) promote use of this knowledge base by health care providers, researchers, industry, government, and the public for making decisions involving the use of genetic tests and services for disease prevention and health promotion (34-35).
II. Evaluati