Submitted to: Book Chapter
Publication Type: Book / chapter
Publication Acceptance Date: 1/7/2005
Publication Date: 1/3/2006
Citation: Butte, N.F., Bacino, C.A., Cole, S.A., Comuzzie, A.G. 2006. Genetics of childhood obesity. In: Goran, M.I., Sothern, M.S. editors. Handbook of Pediatric Obesity: Etiology, Pathophysiology and Prevention. Boca Raton: CRC Press, Taylor & Francis Group. p. 79-96. Interpretive Summary:
Technical Abstract: Obesity is a complex disease influenced by multiple genetic and environmental factors. Because of its complexity, obesity does not conform to simple Mendelian patterns of inheritance, but displays variable expression. Classical genetic studies on twins, siblings and nuclear families clearly have established the genetic influence on body weight and adiposity. Body weight is regulated and defended by complex, highly redundant physiological systems. In this chapter, intrauterine and postnatal critical periods for the development of obesity will be reviewed. In the early origins of adult diseases hypothesis, it is theorized that an environmental stimulus may occur at a critical period and have a lasting effect on the development of diabetes, cardiovascular diseases and obesity. Two postnatal critical periods for the development of adiposity are the first year of life and puberty. Observations on twins, siblings, nuclear families, and in extended pedigrees have all repeatedly shown that an individual's chances of being obese are increased when he or she has relatives who are also obese. The role of environmental factors in the etiology of childhood obesity is also paramount. Modern environments have unmasked obesity in genetically susceptible individuals. The unraveling of rare monogenic forms of early-onset obesity has advanced our understanding of childhood obesity. Six single gene disorders involved in the leptin-melanocortin pathway cause early-onset morbid obesity. All give rise to voracious hyperphagia and profound childhood obesity. There are also syndromic forms of obesity in which overweight is only one of the physical and developmental anomalies. Positional genetic analyses have led to the identification of causative genetic defects underlying these syndromes. To understand the more common forms of childhood obesity, genome-wide scans and candidate gene studies have been performed. The complex patterns of inheritance, the causative genes and underlying mechanisms of childhood obesity are being unraveled through genomics, quantitative genetics, biochemistry and human physiology and molecular epidemiology.