Gene-environment interactions in the etiology of obesity: defining the fundamentals.

The concept of gene-environment interaction refers to a situation where the response or the adaptation to an environmental factor, a behavior, or a change in behavior is conditional on the genotype of the individual. Of particular interest for our understanding of the etiology of human obesity is the role played by genotype-nutrition and genotype-physical activity interactions. Evidence for the presence of such interaction effects affecting body mass and body composition comes from experimental studies undertaken with pairs of monozygotic twins and with nuclear families. These studies reveal that there are large individual differences in the responsiveness to well-defined energy balance manipulations. Overfeeding as well as negative energy balance protocols indicate that the response to these standardized experimental treatments is strongly influenced by one's genetic background. The genes that are responsible for the individual differences in the sensitivity to alterations in energy balance remain to be fully identified. They are likely to be numerous considering the complexity of the biological systems that are involved in body weight regulation. A number of research designs and technologies are available to identify these genes and to delineate the nature and the extent of the genetic polymorphisms involved. It was the purpose of the workshop to define the conditions under which gene-behavior interaction effects of relevance to human obesity could be reliably identified.