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Diabetes

Fine mapping reveals regulation at T2DM susceptibility loci

Nature Reviews Endocrinology volume 12, page 6 (2016)Cite this article

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Genetic fine mapping of 39 susceptibility loci — defined by genome-wide association studies — in 27,206 individuals with type 2 diabetes mellitus (T2DM) and 57,574 controls, has identified 49 distinct association signals, predominantly mapping to noncoding sequences. Comparison of these signals with chromatin immunoprecipitation sequence data identified a common role for hepatocyte nuclear factor 3β (HNF-3β, encoded by FOXA2) transcription-factor binding in the regulation of gene activity contributing to disease susceptibility. For example, an allelic variant associated with T2DM risk at the MTNR1B gene had higher HNF-3β transcriptional enhancer activity in human pancreatic islet and liver-derived cells than low-risk alleles. HNF-3β binding patterns could inform strategies for future research into the mechanisms underlying T2DM susceptibility.

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References

  1. Gaulton, K. J. et al. Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. Nat. Genet. http://dx.doi.org/10.1038/ng.3437

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  1. Robert Phillips
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Phillips, R. Fine mapping reveals regulation at T2DM susceptibility loci. Nat Rev Endocrinol 12, 6 (2016). https://doi.org/10.1038/nrendo.2015.203

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