Year: 2011
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: To investigate whether associations of common genetic variants recently identified for fasting glucose or insulin levels in nondiabetic adults are detectable in healthy children and adolescents. RESEARCH DESIGN AND METHODS: A total of 16 single nucleotide polymorphisms (SNPs) associated with fasting glucose were genotyped in six studies of children and adolescents of European origin, including over 6,000 boys and girls aged 9-16 years. We performed meta-analyses to test associations of individual SNPs and a weighted risk score of the 16 loci with fasting glucose. RESULTS: Nine loci were associated with glucose levels in healthy children and adolescents, with four of these associations reported in previous studies and five reported here for the first time (GLIS3, PROX1, SLC2A2, ADCY5, and CRY2). Effect sizes were similar to those in adults, suggesting age-independent effects of these fasting glucose loci. Children and adolescents carrying glucose-raising alleles of G6PC2, MTNR1B, GCK, and GLIS3 also showed reduced β-cell function, as indicated by homeostasis model assessment of β-cell function. Analysis using a weighted risk score showed an increase [β (95% CI)] in fasting glucose level of 0.026 mmol/L (0.021-0.031) for each unit increase in the score. CONCLUSIONS: Novel fasting glucose loci identified in genome-wide association studies of adults are associated with altered fasting glucose levels in healthy children and adolescents with effect sizes comparable to adults. In nondiabetic adults, fasting glucose changes little over time, and our results suggest that age-independent effects of fasting glucose loci contribute to long-term interindividual differences in glucose levels from childhood onwards.
Source: Diabetes
DOI: 10.2337/db10-1575
Authors: Adam Barker, Stephen J. Sharp, Nicholas J. Timpson, Nabila Bouatia-Naji, Nicole M. Warrington, Stavroula Kanoni, Lawrence J. Beilin, Soren Brage, Panos Deloukas, David M. Evans, Anders Grontved, Neelam Hassanali, Deborah A. Lawlor, Cecile Lecoeur, Ruth J.F. Loos, Stephen J. Lye, Mark I. McCarthy, Trevor A. Mori, Ndeye Coumba Ndiaye, John P. Newnham, Ioanna Ntalla, Craig E. Pennell, Beate St Pourcain, Inga Prokopenko, Susan M. Ring, Naveed Sattar, Sophie Visvikis-Siest, George V. Dedoussis, Lyle J. Palmer, Philippe Froguel, George Davey Smith, Ulf Ekelund, Nicholas J. Wareham, Claudia Langenberg
Institutions: Addenbrooke's Hospital, MRC Epidemiology Unit, Medical Research Council, University of Bristol, Centre National de la Recherche Scientifique, Institut Pasteur de Lille, Université Lille Nord de France, The University of Western Australia, Wellcome Sanger Institute, Harokopio University of Athens, University of Southern Denmark, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Mount Sinai Hospital, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Centre for Human Genetics, Université Henri Poincaré, University of Glasgow, Ontario Institute for Cancer Research, Hammersmith Hospital, Imperial College London, Örebro University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Awards: G1153816297, G1659787205, ALSPAC: consolidation of a two generation cell line backed resource, for the study of the environment and genetic determinants of health and development from before birth to late puberty., G1924190148, G2179969359, The Avon Longitudinal Study of Parents and Children: An international resource for population genomics and lifecourse epidemiology. Core Programme Support 2011-2013., Maternal overnutrition and offspring fat mass, metabolic and vascular function., Understanding the genetic basis of common human diseases: core funding for the Wellcome Trust Centre for Human Genetics., G7042387311
OpenAlex ID: W2167579038