No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels

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Robert A Scott, Audrey Y Chu, Niels Grarup, Alisa K Manning, Marie-France Hivert, Dmitry Shungin, Anke Tönjes, Ajay Yesupriya, Daniel Barnes, Nabila Bouatia-Naji, Nicole L Glazer, Anne U Jackson, Zoltán Kutalik, Vasiliki Lagou, Diana Marek, Laura J Rasmussen-Torvik, Heather M Stringham, Toshiko Tanaka, Mette Aadahl, Dan E Arking & 87 others Sven Bergmann, Eric Boerwinkle, Lori L Bonnycastle, Stefan R Bornstein, Eric Brunner, Suzannah J Bumpstead, Soren Brage, Olga D Carlson, Han Chen, Yii-Der Ida Chen, Peter S Chines, Francis S Collins, David J Couper, Elaine M Dennison, Nicole F Dowling, Josephine S Egan, Ulf Ekelund, Michael R Erdos, Nita G Forouhi, Caroline S Fox, Mark O Goodarzi, Jürgen Grässler, Stefan Gustafsson, Göran Hallmans, Torben Hansen, Aroon Hingorani, John W Holloway, Frank B Hu, Bo Isomaa, Karen A Jameson, Ingegerd Johansson, Anna Elisabet Jonsson, Torben Jørgensen, Mika Kivimaki, Peter Kovacs, Meena Kumari, Johanna Kuusisto, Markku Laakso, Cécile Lecoeur, Claire Lévy-Marchal, Guo Li, Ruth J F Loos, Valeri Lyssenko, Michael Marmot, Pedro Marques-Vidal, Mario A Morken, Gabriele Müller, Kari E North, James S Pankow, Felicity Payne, Inga Prokopenko, Bruce M Psaty, Frida Renström, Ken Rice, Jerome I Rotter, Denis Rybin, Camilla H Sandholt, Avan A Sayer, Peter Shrader, Peter E H Schwarz, David S Siscovick, Alena Stancáková, Michael Stumvoll, Tanya M Teslovich, Gérard Waeber, Gordon H Williams, Daniel R Witte, Andrew R Wood, Weijia Xie, Michael Boehnke, Cyrus Cooper, Luigi Ferrucci, Philippe Froguel, Leif Groop, W H Linda Kao, Peter Vollenweider, Mark Walker, Richard M Watanabe, Oluf Pedersen, James B Meigs, Erik Ingelsson, Inês Barroso, Jose C Florez, Paul W Franks, Josée Dupuis, Nicholas J Wareham, Claudia Langenberg

Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (ß = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (ß = 0.06-0.12 mmol/allele, P = 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P = 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.
Original languageEnglish
JournalDiabetes
Volume61
Issue number5
Pages (from-to)1291-6
Number of pages6
ISSN0046-0192
DOIs
Publication statusPublished - 2012

ID: 38334757