Genes and Obesity: Is There Reason To Change Our Behaviors?

• Obesity
• Genetic predisposition to disease
• Social environment
• Energy metabolism
• Behavior

Several major factors—energy requirements, nutrient partitioning, dietary intake, and physical activity—interact to contribute to the development of obesity. Each factor is influenced by our genotypes. For example, cross-sectional and longitudinal studies show familial resemblance in adiposity, and adoption and twin studies offer clear evidence of a genetic component in human obesity (1-3). It is estimated that 40% to 70% of the within-population variation in obesity is heritable (4). Unfortunately, readers too often mistakenly interpret such reports of high heritability estimates as an indication that genes play a deterministic role in causing obesity, independent of the environment and of behaviors. In contrast, behavioral geneticists have provided mathematical expressions indicating the important role of environmental and behavioral factors in determining body weight despite the fairly high heritability of relative body weight (5).

Our genes can create an energy imbalance and influence weight gain in two primary ways: by contributing to our susceptibility for overeating despite normal energy requirements and by contributing to low energy requirements despite a normal drive to eat. In the first possibility, genetic factors might influence appetite and regulate food intake through many pathways (6). However, cases of genetic syndromes of obesity due to lack of appetite control, such as the Prader-Willi syndrome or leptin deficiency, are rare. Only five cases of leptin deficiency have been reported, two of which were in young cousins from a consanguineous family who had a homozygous frame-shift mutation in the leptin gene (7). …