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Type: Journal article
Title: Association of genetic loci with glucose levels in childhood and adolescence: a meta-analysis of over 6,000 children
Author: Barker, A.
Sharp, S.
Timpson, N.
Bouatia-Naji, N.
Warrington, N.
Kanoni, S.
Beilin, L.
Brage, S.
Deloukas, P.
Evans, D.
Grontved, A.
Hassanali, N.
Lawlor, D.
Lecoeur, C.
Loos, R.
Lye, S.
McCarthy, M.
Mori, T.
Coumba Ndiaye, N.
Newnham, J.
et al.
Citation: Diabetes, 2011; 60(6):1805-1812
Publisher: American Diabetes Association
Issue Date: 2011
ISSN: 0012-1797
Statement of
Adam Barker ... Lyle J. Palmer .. et al.
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.
Keywords: Humans
Blood Glucose
DNA-Binding Proteins
Homeodomain Proteins
Tumor Suppressor Proteins
Transcription Factors
Repressor Proteins
Polymorphism, Single Nucleotide
Glucose Transporter Type 2
Genome-Wide Association Study
Genetic Loci
Adenylyl Cyclases
Germinal Center Kinases
Protein Serine-Threonine Kinases
Rights: © 2011 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See -nc-nd/3.0/ for details.
DOI: 10.2337/db10-1575
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