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Mechanisms of Disease: genetic insights into the etiology of type 2 diabetes and obesity

Nature Clinical Practice Endocrinology & Metabolism volume 4, pages 156–163 (2008)Cite this article

Abstract

Until recently, progress in identification of the genetic variants influencing predisposition to common forms of diabetes and obesity has been slow, a sharp contrast to the large number of genes implicated in rare monogenic forms of both conditions. Recent advances have transformed the situation, however, enabling researchers to undertake well-powered scans able to detect association signals across the entire genome. For type 2 diabetes, the six high-density genome-wide association studies so far performed have extended the number of loci harboring common variants implicated in diabetes susceptibility into double figures. One of these loci, mapping to the fat mass and obesity associated gene (FTO), influences diabetes risk through a primary effect on fat mass, making this the first common variant known to influence weight and individual risk of obesity. These findings offer two main avenues for clinical translation. First, the identification of new pathways involved in disease predisposition—for example, those influencing zinc transport and pancreatic islet regeneration in the case of type 2 diabetes—offers opportunities for development of novel therapeutic and preventative approaches. Second, with continuing efforts to identify additional genetic variants, it may become possible to use patterns of predisposition to tailor individual management of these conditions.

Key Points

  • Genome-wide scans to detect evidence of association between common DNA variants and common disease are now technically possible

  • Application of these methods to type 2 diabetes and obesity has led to identification of several novel genes that influence predisposition to these conditions and highlighted a number of entirely new etiological pathways

  • The expectation is that these methods will contribute to the development of novel therapeutic strategies and, in the future, to efforts to use individual genetic profiling in the clinical management of these conditions

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Acknowledgements

We would like to acknowledge the Throne-Holst Foundation and Diabetes UK. CM Lindgren is a Scientific Leadership Fellow at the Nuffield Department of Medicine at the University of Oxford.

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Authors and Affiliations

  1. CM Lindgren is a Scientific Leadership Fellow at the Wellcome Trust Centre for Human Genetics at the University of Oxford, and MI McCarthy is the Robert Turner Professor of Diabetes, at the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.,

    Cecilia M Lindgren & Mark I McCarthy

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Correspondence to Mark I McCarthy.

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Lindgren, C., McCarthy, M. Mechanisms of Disease: genetic insights into the etiology of type 2 diabetes and obesity. Nat Rev Endocrinol 4, 156–163 (2008). https://doi.org/10.1038/ncpendmet0723

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