The Environmental Genome Project: suggestions and concerns.

The purpose of the meeting was to facilitate a free exchange of information about the Environmental Genome Project among "a diverse group of scientists working in the areas of genetics, gene-environment interactions , molecular epidemiology, and issues of genetic testing" (1). After attending this meeting and reading the recent reports on the Environmental Genome Project in Science (2) and Nature (3), we are concerned that several important issues of interest to the readers of Environmental Health Perspectives are not being adequately addressed by the NIEHS. The goal of the Environmental Genome Project is to "facilitate identification of functionally important polymor-phisms in environment response genes that may determine differences in disease risks to environmental exposures" (1). To this end, the NIEHS proposes to establish a repository of 1,000 anonymous DNA samples representing the population of the United States in order to catalog allelic variants in 200 genes and foster epidemio-logic studies of gene-environment interactions in the etiology of human diseases. At the symposium and in the Science article (2), the potential importance of gene-environment interactions in various diseases was recognized and the potential benefits of a central repository of data on a set of critical risk-mediating genes were clearly enunciated. Two issues, however, have not been adequately addressed: sample size and public policy implications. We have serious doubts that the Environmental Genome Project's proposed sample size of 1,000 individuals is large enough to provide stable estimates of allele frequencies in subgroups of the population. Many of the most promising candidate susceptibility genes have allelic variations that affect less than 5% of the population, and the prevalence of many of these polymorphisms differs markedly among ethnic groups. If 1% of the people in the U.S. population carry a polymorphism for a certain gene, for example , we would expect 10 individuals out of the 1,000 individuals in the study to carry that polymorphism. Ifthose 10 are then to be subdivided into gender/racial/ethnic/sub-groups, the sample size is dearly inadequate to provide precise estimates of the prevalence of the polymorphism in the subgroups. Yet precise estimates of the population prevalence are exactly the kind of information needed by epidemiologists planning studies ofthe role of such genes in disease etiologies. That information is often difficult to find or nonexistent in the current literature, much of which is characterized by small, nonpopulation-based studies that are difficult to generalize. It is difficult to conceive why the Environmental …