ternal or paternal effects could not be identified. Using a new approach to twin studies, Segal and Allison (2002) concluded that common environmental effects might account for approximately 25 percent of the BMI variance in twins. It is important to note the difficulty in assigning proportionality to what is a gene-person-environment interaction.
Similarly, despite its intensity, the search for the specific genes responsible for an individual’s obese status has also been difficult. More than 400 genes, markers, and chromosomal regions have been linked to obesity phenotypes, 208 quantitative trait loci for human obesity have been identified, and 41 Mendelian disorders manifesting obesity have been genomically mapped (Snyder et al., 2004). However, only six single-gene defects resulting in obesity have been found, and in fewer than 150 individuals (Snyder et al., 2004). Thus, even though these monogenetic disorders have provided significant insight into the pathophysiology of obesity (Cummings and Schwartz, 2003; O’Rahilly et al., 2003), with few exceptions, human obesity appears to be a complex genetic trait. Nonetheless, genome-wide scans in widely varying populations have identified several genomic regions containing common quantitative trait loci for obesity phenotypes, suggesting that there may be shared genetic factors predisposing individuals of different ethnic origins to excessive storage of body fat (Bouchard et al., 2003). What is clear, however, is that the genetic characteristics of human populations have not changed in the last three decades, while the prevalence of obesity has approximately doubled. Thus, the recent population rise in body weight reflects the interaction of genotypes that predispose individuals to obesity with detrimental behavioral and environmental factors.
In animals, the evidence is strong for such gene-environment interactions affecting body weight and energy balance (Barsh et al., 2000), with the responsible genes orchestrating a complex system of biological feedback. In this system, central nervous system signals integrate messages about energy intake sent from the gastrointestinal tract with information about the current status of fuel reserves received from the energy-storing adipose tissue. The result is the direction of ingested food either into storage as fat or dissipation as energy, depending on the body’s status and needs at the time (Rosenbaum and Leibel, 1998; Havel, 2000, 2004; Druce and Bloom, 2003; Gale et al., 2004). What now seems clear is that this system evolved to defend the body from excessive energy deficit, a defense mechanism that has far less relevance today, when many humans are exposed to situations of food excess (Schwartz et al., 2003; Havel, 2004). Furthermore, although the system has now been characterized extensively in rodents and in adult humans, little is known about its development during the fetal period, infancy, or childhood (Box 3-3).