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

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

Published Web Location

https://doi.org/10.2337/db11-0973
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) × 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 (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.

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