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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

Journal article published in 2012 by Robert A. Scott, Loïc Yengo, Wei Zhao, Eco J. C. de Geus, Cornelia M. van Duijn, Ulf de Faire, Pim van der Harst, Tatijana Zemunik, Rp P. Welch, Ryan P. Welch, May E. Montasser, Rona J. Strawbridge, Rj J. Strawbridge ORCID, Willems Sm, Vasiliki Lagou and other authors.
This paper is available in a repository.
This paper is available in a repository.

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Abstract

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.