Scott RA, Chu AY, Grarup N, Manning AK, Hivert MF, Shungin D, Tönjes A, Yesupriya A, Barnes D, Bouatia-Naji N, Glazer NL, Jackson AU, Kutalik Z, Lagou V, Marek D, Rasmussen-Torvik LJ, Stringham HM, Tanaka T, Aadahl M, Arking DE, Bergmann S, Boerwinkle E, Bonnycastle LL, Bornstein SR, Brunner E, Bumpstead SJ, Brage S, Carlson OD, Chen H, Chen YD, Chines PS, Collins FS, Couper DJ, Dennison EM, Dowling NF, Egan JS, Ekelund U, Erdos MR, Forouhi NG, Fox CS, Goodarzi MO, Grässler J, Gustafsson S, Hallmans G, Hansen T, Hingorani A, Holloway JW, Hu FB, Isomaa B, Jameson KA, Johansson I, Jonsson A, Jørgensen T, Kivimaki M, Kovacs P, Kumari M, Kuusisto J, Laakso M, Lecoeur C, Lévy-Marchal C, Li G, Loos RJ, Lyssenko V, Marmot M, Marques-Vidal P, Morken MA, Müller G, North KE, Pankow JS, Payne F, Prokopenko I, Psaty BM, Renström F, Rice K, Rotter JI, Rybin D, Sandholt CH, Sayer AA, Shrader P, Schwarz PE, Siscovick DS, Stancáková A, Stumvoll M, Teslovich TM, Waeber G, Williams GH, Witte DR, Wood AR, Xie W, Boehnke M, Cooper C, Ferrucci L, Froguel P, Groop L, Kao WH, Vollenweider P, Walker M, Watanabe RM, Pedersen O, Meigs JB, Ingelsson E, Barroso I, Florez JC, Franks PW, Dupuis J, Wareham NJ, Langenberg C
Diabetes 61 (5) 1291-1296 [2012-05-00; online 2012-03-15]
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.