Publication: A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Publié dans:

Auteurs: Alisa K. Manning, Marie-France Hivert, Robert A. Scott, Jonna L. Grimsby, Nabila Bouatia-Naji, Han Chen, Denis Rybin, Ching-Ti Liu, Lawrence F. Bielak, Inga Prokopenko, Najaf Amin, Daniel Barnes, Gemma Cadby, Jouke-Jan Hottenga, Erik Ingelsson, Anne U. Jackson, Toby Johnson, Stavroula Kanoni, Claes Ladenvall, Vasiliki Lagou, Jari Lahti, Cécile Lecoeur, Yongmei Liu, Maria Teresa Martinez-Larrad, May E. Montasser, Pau Navarro, John R. B. Perry, Laura J. Rasmussen-Torvik, Perttu Salo, Naveed Sattar, Dmitry Shungin, Rona J. Strawbridge, Toshiko Tanaka, Cornelia M. van Duijn, Ping An, Mariza de Andrade, Jeanette S. Andrews, Thor Aspelund, Mustafa Atalay, Yurii Aulchenko, Beverley Balkau, Stefania Bandinelli, Jacques S. Beckmann, John P. Beilby, Claire Bellis, Richard N. Bergman, John Blangero, Mladen Boban, Michael Boehnke, Eric Boerwinkle, Lori L. Bonnycastle, Dorret I. Boomsma, Ingrid B. Borecki, Yvonne Boettcher, Claude Bouchard, Eric Brunner, Danijela Budimir, Harry Campbell, Olga Carlson, Peter S. Chines, Robert Clarke, Francis S. Collins, Arturo Corbatón-Anchuelo, David Couper, Ulf de Faire, George V. Dedoussis, Panos Deloukas, Maria Dimitriou, Josephine M. Egan, Gudny Eiriksdottir, Michael R. Erdos, Johan G. Eriksson, Elodie Eury, Luigi Ferrucci, Ian Ford, Nita G. Forouhi, Caroline S. Fox, Maria Grazia Franzosi, Paul W. Franks, Timothy M. Frayling, Philippe Froguel, Pilar Galan, Eco de Geus, Bruna Gigante, Nicole L. Glazer, Anuj Goel, Leif Groop, Vilmundur Gudnason, Goeran Hallmans, Anders Hamsten, Ola Hansson, Tamara B. Harris, Caroline Hayward, Simon Heath, Serge Hercberg, Andrew A. Hicks, Aroon Hingorani, Albert Hofman, Jennie Hui, Joseph Hung

Résumé

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 x 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

Lien vers HAL – inrae-02650726

Lien vers le DOI – 10.1038/ng.2274