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Open chromatin and diabetes risk

Nature Genetics volume 42, pages 190–192 (2010)Cite this article

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A new study has identified a large number of open chromatin regions harboring active regulatory elements in human pancreatic islets. A type 2 diabetes–associated SNP in TCF7L2 was found to be located in a region of allele-specific open chromatin and shows allele-specific enhancer activity, suggesting a potential mechanism for this disease association.

The prevalence of type 2 diabetes (T2D) has increased rapidly worldwide over the past several decades, a phenomenon that has been ascribed to the collision between an inherited predisposition and a westernized environment. Although the disease is characterized by impairments in both the secretion and the action of insulin, an inability of pancreatic beta-cells to increase insulin secretion so as to compensate for a decrease in insulin action precedes disease onset1. Though the pancreatic islets have been implicated in pathogenesis of the disease, the underlying mechanisms remain poorly understood, and there has been considerable interest in using genetics to characterize them. A number of genetic variants predisposing to type 2 diabetes have been identified through whole-genome association studies2, but for most of them, the mechanisms by which they increase disease risk is unknown. Many of the SNPs reside in noncoding regions, and many affect transcription factors. Exploring transcriptional mechanisms could represent an important approach to the problem. On page 255 of this issue, Jason Lieb and colleagues3 provide a map of open chromatin in human pancreatic islets and show that this information can yield useful insights into T2D-associated loci.

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Figure 1: Model for the chromatin state and mechanism for the TCF7L2 association to type-2 diabetes.

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  1. Leif Groop is in the Department of Clinical Sciences, Diabetes and Endocrinology Unit and Lund University Diabetes Centre, Lund University, University Hospital Malmö, 20502 Malmö, Sweden.,

    Leif Groop

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  1. Leif Groop
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Correspondence to Leif Groop.

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Groop, L. Open chromatin and diabetes risk. Nat Genet 42, 190–192 (2010). https://doi.org/10.1038/ng0310-190

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