Robert A Scott, Audrey Y Chu, Niels Grarup, Alisa K Manning, Marie-France Hivert, Dmitry Shungin, Anke Tönjes, Ajay Yesupriya, Daniel Barnes, Nabila Bouatia-Naji, Nicole L Glazer, Anne U Jackson, Zoltán Kutalik, Vasiliki Lagou, Diana Marek, Laura J Rasmussen-Torvik, Heather M Stringham, Toshiko Tanaka, Mette Aadahl, Dan E Arking & 87 others
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 (ß = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (ß = 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.
|Number of pages||6|
|Publication status||Published - 2012|