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

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. ArkingSven 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 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 Stančáková, 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

Research output: Contribution to journalArticle

Abstract

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) X BMI and SNP X 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 (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10 -6). All SNPs were associated with 2-h glucose (β = 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 (US)
Pages (from-to)1291-1296
Number of pages6
JournalDiabetes
Volume61
Issue number5
DOIs
StatePublished - May 1 2012

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Scott, R. A., Chu, A. Y., Grarup, N., Manning, A. K., Hivert, M. F., Shungin, D., Tönjes, A., Yesupriya, A., Barnes, D., Bouatia-Naji, N., Glazer, N. L., Jackson, A. U., Kutalik, Z., Lagou, V., Marek, D., Rasmussen-Torvik, L. J., Stringham, H. M., Tanaka, T., Aadahl, M., ... Langenberg, C. (2012). No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels. Diabetes, 61(5), 1291-1296. https://doi.org/10.2337/db11-0973