No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels
Authors: 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 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 H. , 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 B. , Ingelsson Erik , Barroso Inês , Florez Jose C. , Franks Paul W. , Dupuis Josée , Wareham Nicholas J. , Langenberg Claudia 
Published: March 2012

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 &gt; 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.