Genetic variation and statistical considerations in relation to overfeeding and underfeeding in humans

The application of genomic approaches to nutritional research and practice offers the possibility to gain greater understanding of genetic variations underlying problems of body weight control in humans. Ideally, these types of gene X environment interaction studies should promote the development of individualized prevention and therapeutic strategies by defining gene polymorphisms that predispose individuals to extremes of energy imbalance. These types of genomic approaches (and genetic counseling) may be useful in the early identification of individuals predisposed to problems of obesity. The ultimate goal would be early intervention (with dietary, exercise, and/or pharmacologic approaches) in an effort to reduce an individual's risk for obesity and associated comorbidities. Of similar public health importance is the use of nutritional genomic approaches to identify individuals who are at reduced risk for developing metabolic complications. Thus, nutritional genomic approaches could be useful not only in examining susceptibility to disease risk but also in identifying individuals who have reduced risk for the development of nutritional disorders. At this point, however, there is relatively little consensus as to the family of genes that render an individual susceptible to weight gain and weight regain or even protect individuals from metabolic disturbances. This is due in part to the challenge of integrating genetic information into physiologic studies and the complexity of body weight regulation. Nonetheless, as molecular mechanisms underlying nutritionally based diseases continue to be uncovered, nutritional practice will need to be modified to reflect advances in our understanding of the genetic basis of body weight regulation.