No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels

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No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels

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Title: No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels
Author: Scott, Robert A.; Chu, Audrey Yu-lei; 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; 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 J.F.; 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 E.H.; Siscovick, David S.; Stančáková, Alena; Stumvoll, Michael; Teslovich, Tanya M.; Waeber, Gérard; Williams, Gordon Harold; Witte, Daniel R.; Wood, Andrew R.; Xie, Weijia; Boehnke, Michael; Cooper, Cyrus; Ferrucci, Luigi; Froguel, Philippe; Groop, Leif; Kao, W.H. Linda; Vollenweider, Peter; Walker, Mark; Watanabe, Richard M.; Pedersen, Oluf; Meigs, James Benjamin; Ingelsson, Erik; Barroso, Inês; Florez, Jose Carlos; Franks, Paul W.; Dupuis, Josée; Wareham, Nicholas J.; Langenberg, Claudia

Note: Order does not necessarily reflect citation order of authors.

Citation: Scott, Robert A., Audrey Y. Chu, Niels Grarup, Alisa K. Manning, Marie-France Hivert, Dmitry Shungin, Anke Tönjes, et al. 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.
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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.
Published Version: doi:10.2337/db11-0973
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