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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways |
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| Authors: | Robert A Scott Vasiliki Lagou Ryan P Welch Eleanor Wheeler May E Montasser Jian'an Luan Reedik Mägi Rona J Strawbridge Emil Rehnberg Stefan Gustafsson Stavroula Kanoni Laura J Rasmussen-Torvik Loïc Yengo Cecile Lecoeur Dmitry Shungin Serena Sanna Carlo Sidore Paul C D Johnson J Wouter Jukema Toby Johnson Anubha Mahajan Niek Verweij Gudmar Thorleifsson Jouke-Jan Hottenga Sonia Shah Albert V Smith Bengt Sennblad Christian Gieger Perttu Salo Markus Perola Nicholas J Timpson David M Evans Beate St Pourcain Ying Wu Jeanette S Andrews Jennie Hui Lawrence F Bielak Wei Zhao Momoko Horikoshi |
| Institution: | 1] Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK. [2]. |
| 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. |
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