Commentary: Epidemiology and the Continuum from Genetic Research to Genetic Testing

In January 2001, the Centers for Disease Control and Prevention and the National Institutes of Health convened an expert panel to develop recommendations for evaluating and synthesizing data from epidemiologic studies of the human genome. Experts in medicine, genetics, epidemiology, statistics, laboratory sciences, prevention effectiveness, and the social sciences discussed examples drawn from cancer, cardiovascular disease, human immunodeficiency virus infection, and other areas. Participants discussed issues for evaluating and synthesizing data from epidemiologic and genetic test studies (table 1) relevant to three areas: 1) prevalence of gene variants and gene-disease associations, 2) geneenvironment and gene-gene interactions, and 3) evaluation of genetic tests. The workshop recommendations in areas 1 and 3 are included in this issue of the Journal (1, 2). The recommendations of area 2 (gene-environment interaction) are in progress (D. J. Hunter, Channing Laboratory, unpublished manuscript). I summarize the meeting’s background and highlight the importance of the panel’s recommendations. Many scientists believe that advances in human genetics and the Human Genome Project will play a central role in the practice of medicine and public health in the 21st century by predicting and preventing disease and promoting health (3). However, to ensure a systematic translation of genetic research into clinical practice, ongoing epidemiologic data are needed, in addition to studies of gene function and biologic pathways, to quantify the impact of gene variants on the risk of various diseases and to identify and quantify the impact of modifiable risk factors that interact with gene variants (4). So far, most studies in this area come from family-based studies or highly selected groups. Results from population-based studies will help medical and public health professionals better target medical, behavioral, and environmental interventions. A systematic application of epidemiologic methods and approaches to the human genome—HuGE (4)—represents the continuum from gene discovery (traditional domain of genetic epidemiology) to risk characterization (domain of molecular epidemiology) and evaluation of genetic tests and services (applied epidemiology and health services research). As a multidisciplinary field, epidemiology has begun to address issues related to post-gene discovery with increasing emphasis on characterization of gene effects and genetic tests in populations (what do you do with a gene after you find one?). The continuum of studies can be divided into the three areas that are the topics of the workshop papers: 1) assessing the population prevalence of gene variants and evaluating genotype-disease associations; 2) assessing the impact of gene-environment and gene-gene interaction on disease risk; and 3) evaluating the usefulness and impact of genetic tests in populations. Because of the numerous genes that are discovered on a regular basis, an epidemiologic approach is needed for all three study domains. An analysis of the published epidemiologic literature on human genes for 2001 reveals that, of the 2,042 published articles, most reported on only the population prevalence of gene variants or simple gene-disease associations (82.0 percent), while 14.5 percent integrated the study of interactions (gene-gene and gene-environment) and only 3.5 percent dealt with evaluation of genetic tests (5). Epidemiologic studies of geneenvironment interaction and genetic tests are bound to increase as more genes are discovered, characterized, and used to develop diagnostic and predictive tests.