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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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