Monday, January 01, 2007

Genetics of Obesity

In this review of the genetics of obesity, the authors review the genetics of monogenic obesity, syndromic obesity, and polygenic obesity. The gist is that some progress has been made but we will have to mainly focus more on GxE interactions and this will be immensely complex as the picture on the left shows. I'm not sure if they mentioned population-based approaches but it would seem that that would hold some promise.

Unraveling the Genetics of Human Obesity

David M. Mutch, Karine Clément

PLoS Genetics December 2006, v. 2(12)

Abstract: The use of modern molecular biology tools in deciphering the perturbed biochemistry and physiology underlying the obese state has proven invaluable. Identifying the hypothalamic leptin/melanocortin pathway as critical in many cases of monogenic obesity has permitted targeted, hypothesis-driven experiments to be performed, and has implicated new candidates as causative for previously uncharacterized clinical cases of obesity. Meanwhile, the effects of mutations in the melanocortin-4 receptor gene, for which the obese phenotype varies in the degree of severity among individuals, are now thought to be influenced by one's environmental surroundings. Molecular approaches have revealed that syndromes (Prader-Willi and Bardet-Biedl) previously assumed to be controlled by a single gene are, conversely, regulated by multiple elements. Finally, the application of comprehensive profiling technologies coupled with creative statistical analyses has revealed that interactions between genetic and environmental factors are responsible for the common obesity currently challenging many Westernized societies. As such, an improved understanding of the different “types” of obesity not only permits the development of potential therapies, but also proposes novel and often unexpected directions in deciphering the dysfunctional state of obesity.

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