The human genome project is complete. How do we develop a handle for the pump?

Abstract

A half century since the publication of the structure of the DNA molecule (2), the sequence of the human genome is complete. Some expect this achievement to be translated into advances in medicine and public health relatively rapidly (3– 6). Proponents of this approach tend to focus on the potential to tailor primary prevention, secondary prevention, or therapy on the basis of genetic information. It is also possible that a better understanding of genetic effects and gene­ environment interactions in disease processes will allow us to develop better interventions, such as avoidance of defined exposures and chemoprevention, to apply to the general population (7). Others are more skeptical (8–13). A key element in translation will be the application of epidemio­ logic studies to evaluate the role of genetic variants in the etiology of human disease (1). There has been a tremendous increase in the number and scope of peer-reviewed articles on human genome epidemiology, which has generated in turn the challenge of integrating these data, and this has led to many reviews of gene-disease associations and to gene­ gene and gene-environment interaction in response. The purpose of this article is to provide an overview of the expe­ rience gained in integrating evidence in the Human Genome Epidemiology (HuGE) reviews and to suggest changes that may encourage more investigators to contribute reviews and to respond to changes in the character of the evidence. HuGE reviews were established as a means of integrating evidence from human genome epidemiologic studies, that is, population-based studies of the impact of human genetic variation on health and disease (14). HuGE reviews are systematic, peer-reviewed synopses of epidemiologic aspects of human genes, including prevalence of allelic vari­ ants in different populations, population-based information on disease risk, evidence for gene-environment interaction, and quantitative data on genetic tests and services. They are carried out according to specified guidelines (15). As of February 2003, 20 such reviews have been published (table