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

TY - JOUR

T1 - No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels

AU - Scott, Robert A.

AU - Chu, Audrey Y.

AU - Grarup, Niels

AU - Manning, Alisa K.

AU - Hivert, Marie-France

AU - Shungin, Dmitry

AU - Toenjes, Anke

AU - Yesupriya, Ajay

AU - Barnes, Daniel

AU - Bouatia-Naji, Nabila

AU - Glazer, Nicole L.

AU - Jackson, Anne U.

AU - Kutalik, Zoltan

AU - Lagou, Vasiliki

AU - Marek, Diana

AU - Rasmussen-Torvik, Laura J.

AU - Stringham, Heather M.

AU - Tanaka, Toshiko

AU - Aadahl, Mette

AU - Arking, Dan E.

AU - Bergmann, Sven

AU - Boerwinkle, Eric

AU - Bonnycastle, Lori L.

AU - Bornstein, Stefan R.

AU - Brunner, Eric

AU - Bumpstead, Suzannah J.

AU - Brage, Soren

AU - Carlson, Olga D.

AU - Chen, Han

AU - Chen, Yii-Der Ida

AU - Chines, Peter S.

AU - Collins, Francis S.

AU - Couper, David J.

AU - Dennison, Elaine M.

AU - Dowling, Nicole F.

AU - Egan, Josephine S.

AU - Ekelund, Ulf

AU - Erdos, Michael R.

AU - Forouhi, Nita G.

AU - Fox, Caroline S.

AU - Goodarzi, Mark O.

AU - Graessler, Juergen

AU - Gustafsson, Stefan

AU - Hallmans, Goeran

AU - Hansen, Torben

AU - Hingorani, Aroon

AU - Holloway, John W.

AU - Hu, Frank B.

AU - Isomaa, Bo

AU - Jameson, Karen A.

AU - Johansson, Ingegerd

AU - Jonsson, Anna

AU - Jorgensen, Torben

AU - Kivimaki, Mika

AU - Kovacs, Peter

AU - Kumari, Meena

AU - Kuusisto, Johanna

AU - Laakso, Markku

AU - Lecoeur, Cecile

AU - Levy-Marchal, Claire

AU - Li, Guo

AU - Loos, Ruth J. F.

AU - Lyssenko, Valeriya

AU - Marmot, Michael

AU - Marques-Vidal, Pedro

AU - Morken, Mario A.

AU - Mueller, Gabriele

AU - North, Kari E.

AU - Pankow, James S.

AU - Payne, Felicity

AU - Prokopenko, Inga

AU - Psaty, Bruce M.

AU - Renström, Frida

AU - Rice, Ken

AU - Rotter, Jerome I.

AU - Rybin, Denis

AU - Sandholt, Camilla H.

AU - Sayer, Avan A.

AU - Shrader, Peter

AU - Schwarz, Peter E. H.

AU - Siscovick, David S.

AU - Stancakova, Alena

AU - Stumvoll, Michael

AU - Teslovich, Tanya M.

AU - Waeber, Gerard

AU - Williams, Gordon H.

AU - Witte, Daniel R.

AU - Wood, Andrew R.

AU - Xie, Weijia

AU - Boehnke, Michael

AU - Cooper, Cyrus

AU - Ferrucci, Luigi

AU - Froguel, Philippe

AU - Groop, Leif

AU - Kao, W. H. Linda

AU - Vollenweider, Peter

AU - Walker, Mark

AU - Watanabe, Richard M.

AU - Pedersen, Oluf

AU - Meigs, James B.

AU - Ingelsson, Erik

AU - Barroso, Ines

AU - Florez, Jose C.

AU - Franks, Paul

AU - Dupuis, Josee

AU - Wareham, Nicholas J.

AU - Langenberg, Claudia

PY - 2012

Y1 - 2012

N2 - 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) X BMI and SNP x 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 (beta = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 X 10(-6)). All SNPs were associated with 2-h glucose (beta = 0.06-0.12 mmol/allele, P <= 1.53 X 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. Diabetes 61:1291-1296, 2012

AB - 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) X BMI and SNP x 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 (beta = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 X 10(-6)). All SNPs were associated with 2-h glucose (beta = 0.06-0.12 mmol/allele, P <= 1.53 X 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. Diabetes 61:1291-1296, 2012

U2 - 10.2337/db11-0973

DO - 10.2337/db11-0973

M3 - Article

VL - 61

SP - 1291

EP - 1296

JO - Diabetes

JF - Diabetes

SN - 1939-327X

IS - 5

ER -