Association of genetic loci with glucose levels in childhood and adolescence: A meta-analysis of over 6,000 children

Barker, Adam, Sharp, Stephen J., Timpson, Nicholas J., Bouatia-Naji, Nabila, Warrington, Nicole M., Kanoni, Stavroula, Beilin, Lawrence J., Brage, Soren, Deloukas, Panos, Evans, David M., Grontved, Anders, Hassanali, Neelam, Lawlor, Deborah A., Lecoeur, Cecile, Loos, Ruth J.F., Lye, Stephen J., McCarthy, Mark I., Mori, Trevor A., Ndiaye, Ndeye Coumba, Newnham, John P., Ntalla, Ioanna, Pennell, Craig E., St Pourcain, Beate, Prokopenko, Inga, Ring, Susan M., Sattar, Naveed, Visvikis-Siest, Sophie, Dedoussis, George V., Palmer, Lyle J., Froguel, Philippe, Smith, George Davey, Ekelund, Ulf, Wareham, Nicholas J. and Langenberg, Claudia (2011) Association of genetic loci with glucose levels in childhood and adolescence: A meta-analysis of over 6,000 children. Diabetes, 60 6: 1805-1812. doi:10.2337/db10-1575


Author Barker, Adam
Sharp, Stephen J.
Timpson, Nicholas J.
Bouatia-Naji, Nabila
Warrington, Nicole M.
Kanoni, Stavroula
Beilin, Lawrence J.
Brage, Soren
Deloukas, Panos
Evans, David M.
Grontved, Anders
Hassanali, Neelam
Lawlor, Deborah A.
Lecoeur, Cecile
Loos, Ruth J.F.
Lye, Stephen J.
McCarthy, Mark I.
Mori, Trevor A.
Ndiaye, Ndeye Coumba
Newnham, John P.
Ntalla, Ioanna
Pennell, Craig E.
St Pourcain, Beate
Prokopenko, Inga
Ring, Susan M.
Sattar, Naveed
Visvikis-Siest, Sophie
Dedoussis, George V.
Palmer, Lyle J.
Froguel, Philippe
Smith, George Davey
Ekelund, Ulf
Wareham, Nicholas J.
Langenberg, Claudia
Title Association of genetic loci with glucose levels in childhood and adolescence: A meta-analysis of over 6,000 children
Journal name Diabetes   Check publisher's open access policy
ISSN 0012-1797
1939-327X
Publication date 2011-04
Sub-type Article (original research)
DOI 10.2337/db10-1575
Open Access Status
Volume 60
Issue 6
Start page 1805
End page 1812
Total pages 8
Place of publication Alexandria, United States
Publisher American Diabetes Association
Language eng
Subject 2724 Internal Medicine
2712 Endocrinology, Diabetes and Metabolism
Formatted 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 genomewide 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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