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

2012; Nature Portfolio; Volume: 44; Issue: 6 Linguagem: Inglês

10.1038/ng.2274

1546-1718

Man Li, Marie‐France Hivert, Robert A. Scott, Jonna Grimsby, Nabila Bouatia‐Naji, Han Chen, Denis Rybin, Yongmei Liu, Lawrence F. Bielak, Inga Prokopenko, Najaf Amin, Daniel R. Barnes, Gemma Cadby, Jouke‐Jan Hottenga, Erik Ingelsson, Anne Jackson, Toby Johnson, Stavroula Kanoni, Claes Ladenvall, Vasiliki Lagou, Jari Lahti, Cécile Lecœur, Yongmei Liu, Nicholas G. Martin, 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 S. Aulchenko, Beverley Balkau, Stefania Bandinelli, J. Beckmann, John Beilby, Claire Bellis, Richard N. Bergman, John Blangero, Mladen Boban, Michael Boehnke, Eric Boerwinkle, Lori L. Bonnycastle, Dorret I. Boomsma, Ingrid B. Borecki, Yvonne Böttcher, Claude Bouchard, Eric J. Brunner, Danijela Budimir, Harry Campbell, Olga D. Carlson, Peter S. Chines, Robert Clarke, Francis S. Collins, Arturo Corbatón Anchuelo, David Couper, Ulf dé Fairé, George Dedoussis, Panos Deloukas, Maria Dimitriou, Josephine M. Egan, Guðný Eiríksdóttir, 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 J. C. de Geus, Bruna Gigante, Nicole L. Glazer, Anuj Goel, Leif Groop, Vilmundur Guðnason, Göran Hallmans, Anders Hamsten, Ola Hansson, Tamara B. Harris, Caroline Hayward, Simon Heath, Serge Herçberg, Andrew A. Hicks, Aroon D. Hingorani, Albert Hofman, Jennie Hui, Joseph Hung, Marjo‐Riitta Järvelin, Min A. Jhun, P. Johnson, J. Wouter Jukema, Antti Jula, W.H. Linda Kao, Jaakko Kaprio, Sharon L. R. Kardia, Sirkka Keinänen‐Kiukaanniemi, Mika Kivimäki, Ivana Kolčić, Péter Kovács, Meena Kumari, Johanna Kuusisto, Kirsten Ohm Kyvik, Markku Laakso, Timo A. Lakka, Lars Lannfelt, G.M. Lathrop, Lenore J. Launer, Karin Leander, Guo Li, Lars Lind, Jaana Lindström, Stéphane Lobbens, Ruth J. F. Loos, Jian'an Luan, V. Lyssenko, Reedik Mägi, Patrik K. E. Magnusson, Michael Marmot, Pierre Meneton, Karen L. Mohlke, Vincent Mooser, Mario A. Morken, Iva Miljkovic, Narisu Narisu, Jeff O’Connell, Ken K. Ong, Ben A Oostra, Lyle J. Palmer, Aarno Palotie, James S. Pankow, John F. Peden, Nancy L. Pedersen, Marina Pehlić, Leena Peltonen, Brenda W.J.H. Penninx, Marijana Peričić, Markus Perola, Louis Pérusse, Patricia A Peyser, Ozren Polašek, Peter P. Pramstaller, Michael A. Province, Katri Räikkönen, Rainer Rauramaa, Emil Rehnberg, Kenneth Rice, Jerome I. Rotter, Igor Rudan, A Ruokonen, Timo Saaristo, Maria Sabater‐Lleal, Veikko Salomaa, David B. Savage, Richa Saxena, Peter Schwarz, Udo Seedorf, Bengt Sennblad, Manuel Serrano‐Ríos, Alan R. Shuldiner, Eric J.G. Sijbrands, David S. Siscovick, Johannes H. Smit, Kerrin S. Small, Nicholas L. Smith, Albert V. Smith, Alena Stančáková, Kathleen Stirrups, Michael Stümvoll, Yan V. Sun, Amy J. Swift, Anke Tönjes, J. Tuomilehto, Stella Trompet, André G. Uitterlinden, Matti Uusitupa, Max Vikström, Véronique Vitart, Marie‐Claude Vohl, Benjamin F. Voight, Péter Vollenweider, Gérard Waeber, Dawn Waterworth, Hugh Watkins, Eleanor Wheeler, Elisabeth Widén, Philipp S. Wild, Sara M. Willems, Gonneke Willemsen, James F. Wilson, Jacqueline C.M. Witteman, Alan F. Wright, Hanieh Yaghootkar, Diana Zélénika, Tatijana Zemunik, Lina Zgaga, Nicholas J. Wareham, Mark I. McCarthy, Inês Barroso, Richard M. Watanabe, José C. Florez, Josée Dupuis, James B. Meigs, Claudia Langenberg,

Pancreatic function and diabetes

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-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 × 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.