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

Published in:

Authors: Robert A. Scott, Vasiliki Lagou, Ryan P. Welch, Eleanor Wheeler, May E. Montasser, Jian'An Luan, Reedik Maegi, Rona J. Strawbridge, Emil Rehnberg, Stefan Gustafsson, Stavroula Kanoni, Laura J. Rasmussen-Torvik, Loïc Yengo, Cécile 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, Pau Navarro, Aaron Isaacs, Jeffrey R. O'Connell, Kathleen Stirrups, Veronique Vitart, Caroline Hayward, Tonu Esko, Evelin Mihailov, Ross M. Fraser, Tove Fall, Benjamin F. Voight, Soumya Raychaudhuri, Han Chen, Cecilia M. Lindgren, Andrew P. Morris, Nigel W. Rayner, Neil Robertson, Denis Rybin, Ching-Ti Liu, Jacques S. Beckmann, Sara M. Willems, Peter S. Chines, Anne U. Jackson, Hyun Min Kang, Heather M. Stringham, Kijoung Song, Toshiko Tanaka, John F. Peden, Anuj Goel, Andrew A. Hicks, Ping An, Martina Mueller-Nurasyid, Anders Franco-Cereceda, Lasse Folkersen, Letizia Marullo, Hanneke Jansen, Albertine J. Oldehinkel, Marcel Bruinenberg, James S. Pankow, Kari E. North, Nita G. Forouhi, Ruth J. F. Loos, Sarah Edkins, Tibor V. Varga, Goeran Hallmans, Heikki Oksa, Mulas Antonella, Ramaiah Nagaraja, Stella Trompet, Ian Ford, Stephan J. L. Bakker, Augustine Kong, Meena Kumari, Bruna Gigante, Christian Herder, Patricia B. Munroe, Mark Caulfield, Jula Antti, Massimo Mangino, Kerrin Small, Serge Hercberg

Summary

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.

Link to HAL – inrae-02653025

Link to DOI – 10.1038/ng.2385