Abstract
Obesity is a disorder characterized by an excess accumulation of body fat resulting from a mismatch between energy intake and expenditure. Incidence of obesity has increased dramatically in the past few years, almost certainly fuelled by a shift in dietary habits owing to the widespread availability of low-cost, hypercaloric foods. However, clear differences exist in obesity susceptibility among individuals exposed to the same obesogenic environment, implicating genetic risk factors. Numerous genes have been shown to be involved in the development of monofactorial forms of obesity. In genome-wide association studies, a large number of common variants have been associated with adiposity levels, each accounting for only a small proportion of the predicted heritability. Although the small effect sizes of obesity variants identified in genome-wide association studies currently preclude their utility in clinical settings, screening for a number of monogenic obesity variants is now possible. Such regular screening will provide more informed prognoses and help in the identification of at-risk individuals who could benefit from early intervention, in evaluation of the outcomes of current obesity treatments, and in personalization of the clinical management of obesity. This Review summarizes current advances in obesity genetics and discusses the future of research in this field and the potential relevance to personalized obesity therapy.
Key Points
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Individual susceptibility to obesity is strongly influenced by genetic factors
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Rare monogenic obesity variants of large effect size and common variants of small effect sizes collectively account for only a small proportion of the heritability of adiposity
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Several copy number variants, both common and rare, have been shown to contribute to individual variation in BMI and increased risk of obesity
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Genetic variants associated with BMI and obesity identified to date have increased our understanding of the underlying mechanisms by which obesity develops and is maintained
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Screening for monofactorial obesity variants can provide informed prognoses for patients and opportunities for early intervention and treatment of additional pathologies frequently associated with these forms of obesity
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Examination of clinical outcomes of interventions such as bariatric surgery in individuals with genetic susceptibility to obesity could permit personalization of obesity therapy in the future
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Change history
05 November 2013
In the original published version of this article, the chromosomal positions of the loci in Figure 1b were incorrectly ordered. This error has now been corrected for the HTML and PDF versions of the article.
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Acknowledgements
The authors wish to thank S. Saeed and H. Al-Saud (Department of Genomics of Common Disease, Imperial College London, London, United Kingdom W12 0NN) for helpful suggestions and a critical reading of the manuscript.
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J. S. El-Sayed Moustafa and P. Froguel contributed equally to researching the data for the article, discussion of content, and to writing and editing of the manuscript.
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El-Sayed Moustafa, J., Froguel, P. From obesity genetics to the future of personalized obesity therapy. Nat Rev Endocrinol 9, 402–413 (2013). https://doi.org/10.1038/nrendo.2013.57
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DOI: https://doi.org/10.1038/nrendo.2013.57
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