PuSH - Publication Server of Helmholtz Zentrum München: No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels.

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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.* ; Arking, D.E.* ; Bergmann, S.* ; Boerwinkle, E.* ; Bonnycastle, L.L.* ; Bornstein, S.R.* ; Brunner, E.* ; Bumpstead, S.J.* ; Brage, S.* ; Carlson, O.D.* ; Chen, H.* ; Chen, Y.D.* ; Chines, P.S.* ; Collins, F.S.* ; Couper, D.J.* ; Dennison, E.M.* ; Dowling, N.F.* ; Egan, J.S.* ; Ekelund, U.* ; Erdos, M.R.* ; Forouhi, N.G.* ; Fox, C.S.* ; Goodarzi, M.O.* ; Grässler, J.* ; Gustafsson, S.* ; Hallmans, G.* ; Hansen, T.* ; Hingorani, A.* ; Holloway, J.W.* ; Hu, F.B.* ; Isomaa, B.* ; Jameson, K.A.* ; Johansson, I.* ; Jonsson, A.* ; Jørgensen, T.* ; Kivimaki, M.* ; Kovacs, P.* ; Kumari, M.* ; Kuusisto, J.* ; Laakso, M.* ; Lecoeur, C.* ; Lévy-Marchal, C.* ; Li, G.* ; Loos, R.J.* ; Lyssenko, V.* ; Marmot, M.* ; Marques-Vidal, P.* ; Morken, M.A.* ; Müller, G.* ; North, K.E.* ; Pankow, J.S.* ; Payne, F.* ; Prokopenko, I.* ; Psaty, B.M.* ; Renström, F.* ; Rice, K.* ; Rotter, J.I.* ; Rybin, D.* ; Sandholt, C.H.* ; Sayer, A.A.* ; Shrader, P.* ; Schwarz, P.E.* ; Siscovick, D.S.* ; Stancáková, A.* ; Stumvoll, M.* ; Teslovich, T.M.* ; Waeber, G.* ; Williams, G.H.* ; Witte, D.R.* ; Wood, A.R.* ; Xie, W.* ; Boehnke, M.* ; Cooper, C.* ; Ferrucci, L.* ; Froguel, P.* ; Groop, L.* ; Kao, W.H.* ; Vollenweider, P.* ; Walker, M.* ; Watanabe, R.M.* ; Pedersen, O.* ; Meigs, J.B.* ; Ingelsson, E.* ; Barroso, I.* ; Florez, J.C* ; Franks, P.W.* ; Dupuis, J.* ; Wareham, N.J.* ; Langenberg, C.*

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

Diabetes 61, 1291-1296 (2012)

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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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