Genetics of Pathways Regulating Body Weight in the Development of Obesity in Humans

Although rapid globalization of the Westernized way of life is responsible for the large rise in the number of obesity cases (about 1 billion individuals are now overweight or frankly obese), obesity is a typical common multifactorial disease in that environmental and genetic factors interact, resulting in a disease state (1). There is strong evidence for a genetic component to human obesity: e.g., the familial clustering (the relative risk among siblings being 3–7) (2) and the high concordance of body composition in monozygotic twins (3). However, the role of genetic factors in many human obesities (referred to as “common obesity” in this review) is complex, being determined by interaction of several genes (polygenic), each of which may have relatively small effects (i.e., they are “susceptibility” genes and work in combination with each other as well as with environmental factors such as nutrients, physical activity, and smoking).

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