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

Lookup NU author(s): Professor Mark Walker

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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) 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


Publication metadata

Author(s): Scott RA, Chu AY, Grarup N, Manning AK, Hivert MF, Shungin D, Tonjes 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 YDI, Chines PS, Collins FS, Couper DJ, Dennison EM, Dowling NF, Egan JS, Ekelund U, Erdos MR, Forouhi NG, Fox CS, Goodarzi MO, Grassler J, Gustafsson S, Hallmans G, Hansen T, Hingorani A, Holloway JW, Hu FB, Isomaa B, Jameson KA, Johansson I, Jonsson A, Jorgensen T, Kivimaki M, Kovacs P, Kumari M, Kuusisto J, Laakso M, Lecoeur C, Levy-Marchal C, Li G, Loos RJF, Lyssenko V, Marmot M, Marques-Vidal P, Morken MA, Muller G, North KE, Pankow JS, Payne F, Prokopenko I, Psaty BM, Renstrom F, Rice K, Rotter JI, Rybin D, Sandholt CH, Sayer AA, Shrader P, Schwarz PEH, Siscovick DS, Stancakova A, Stumvoll M, Teslovich TM, Waeber G, Williams GH, Witte DR, Wood AR, Xie WJ, Boehnke M, Cooper C, Ferrucci L, Froguel P, Groop L, Kao WHL, Vollenweider P, Walker M, Watanabe RM, Pedersen O, Meigs JB, Ingelsson E, Barroso I, Florez JC, Franks PW, Dupuis J, Wareham NJ, Langenberg C

Publication type: Article

Publication status: Published

Journal: Diabetes

Year: 2012

Volume: 61

Issue: 5

Pages: 1291-1296

Print publication date: 01/05/2012

ISSN (print): 0012-1797

ISSN (electronic): 1939-327X

Publisher: American Diabetes Association

URL: http://dx.doi.org/10.2337/db11-0973

DOI: 10.2337/db11-0973


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Funding

Funder referenceFunder name
G0100222Medical Research Council
G1002084Medical Research Council
G0701863Medical Research Council
G0902037Medical Research Council
MC_U106179473Medical Research Council
MC_UP_A620_1014Medical Research Council
G19/35Medical Research Council
G8802774Medical Research Council
K24 DK080140NIDDK NIH HHS
MC_U106179471Medical Research Council
MC_UP_A100_1003Medical Research Council
MC_UP_A620_1015Medical Research Council
P30 DK020572NIDDK NIH HHS
P30 DK063491NIDDK NIH HHS
R01 DK072041NIDDK NIH HHS
RG/07/008/23674British Heart Foundation
UL1 RR024148NCRR NIH HHS
UL1 TR000124NCATS NIH HHS
T32 HL007575NHLBI NIH HHS
UL1 RR025741NCRR NIH HHS

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