Association of Genetic Loci With Glucose Levels in Childhood and Adolescence A Meta-Analysis of Over 6,000 Children

A. Barker, S. J. Sharp, N. J. Timpson, N. Bouatia-Naji, N. M. Warrington, S. Kanoni, L. J. Beilin, S. Brage, P. Deloukas, D. M. Evans, A. Grontved, N. Hassanali, D. A. Lawlor, C. Lecoeur, R. J. F. Loos, S. J. Lye, M. I. McCarthy, T. A. Mori, N. C. Ndiaye, J. P. Newnham & 14 andre I. Ntalla, C. E. Pennell, B. St Pourcain, I. Prokopenko, S. M. Ring, N. Sattar, S. Visvikis-Siest, G. V. Dedoussis, L. J. Pahner, P. Froguel, G. D. Smith, U. Ekelund, N. J. Wareham, C. Langenberg

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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 p-cell function, as indicated by homeostasis model assessment of beta-cell function. Analysis using a weighted risk score showed an increase [beta (95% CI)] in fasting glucose level of 0.026 mrnol/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. Diabetes 60:1805-1812, 2011
OriginalsprogEngelsk
TidsskriftDiabetes
Vol/bind60
Udgave nummer6
Sider (fra-til)1805-1812
Antal sider8
ISSN0046-0192
DOI
StatusUdgivet - 2011

Citer dette

Barker, A., Sharp, S. J., Timpson, N. J., Bouatia-Naji, N., Warrington, N. M., Kanoni, S., ... Langenberg, C. (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. https://doi.org/10.2337/db10-1575
Barker, A. ; Sharp, S. J. ; Timpson, N. J. ; Bouatia-Naji, N. ; Warrington, N. M. ; Kanoni, S. ; Beilin, L. J. ; Brage, S. ; Deloukas, P. ; Evans, D. M. ; Grontved, A. ; Hassanali, N. ; Lawlor, D. A. ; Lecoeur, C. ; Loos, R. J. F. ; Lye, S. J. ; McCarthy, M. I. ; Mori, T. A. ; Ndiaye, N. C. ; Newnham, J. P. ; Ntalla, I. ; Pennell, C. E. ; St Pourcain, B. ; Prokopenko, I. ; Ring, S. M. ; Sattar, N. ; Visvikis-Siest, S. ; Dedoussis, G. V. ; Pahner, L. J. ; Froguel, P. ; Smith, G. D. ; Ekelund, U. ; Wareham, N. J. ; Langenberg, C. / Association of Genetic Loci With Glucose Levels in Childhood and Adolescence A Meta-Analysis of Over 6,000 Children. I: Diabetes. 2011 ; Bind 60, Nr. 6. s. 1805-1812.
@article{3c3c5326e9394c3ca286119c94be10ee,
title = "Association of Genetic Loci With Glucose Levels in Childhood and Adolescence A Meta-Analysis of Over 6,000 Children",
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 p-cell function, as indicated by homeostasis model assessment of beta-cell function. Analysis using a weighted risk score showed an increase [beta (95{\%} CI)] in fasting glucose level of 0.026 mrnol/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. Diabetes 60:1805-1812, 2011",
author = "A. Barker and Sharp, {S. J.} and Timpson, {N. J.} and N. Bouatia-Naji and Warrington, {N. M.} and S. Kanoni and Beilin, {L. J.} and S. Brage and P. Deloukas and Evans, {D. M.} and A. Grontved and N. Hassanali and Lawlor, {D. A.} and C. Lecoeur and Loos, {R. J. F.} and Lye, {S. J.} and McCarthy, {M. I.} and Mori, {T. A.} and Ndiaye, {N. C.} and Newnham, {J. P.} and I. Ntalla and Pennell, {C. E.} and {St Pourcain}, B. and I. Prokopenko and Ring, {S. M.} and N. Sattar and S. Visvikis-Siest and Dedoussis, {G. V.} and Pahner, {L. J.} and P. Froguel and Smith, {G. D.} and U. Ekelund and Wareham, {N. J.} and C. Langenberg",
year = "2011",
doi = "10.2337/db10-1575",
language = "English",
volume = "60",
pages = "1805--1812",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "6",

}

Barker, A, Sharp, SJ, Timpson, NJ, Bouatia-Naji, N, Warrington, NM, Kanoni, S, Beilin, LJ, Brage, S, Deloukas, P, Evans, DM, Grontved, A, Hassanali, N, Lawlor, DA, Lecoeur, C, Loos, RJF, Lye, SJ, McCarthy, MI, Mori, TA, Ndiaye, NC, Newnham, JP, Ntalla, I, Pennell, CE, St Pourcain, B, Prokopenko, I, Ring, SM, Sattar, N, Visvikis-Siest, S, Dedoussis, GV, Pahner, LJ, Froguel, P, Smith, GD, Ekelund, U, Wareham, NJ & Langenberg, C 2011, 'Association of Genetic Loci With Glucose Levels in Childhood and Adolescence A Meta-Analysis of Over 6,000 Children', Diabetes, bind 60, nr. 6, s. 1805-1812. https://doi.org/10.2337/db10-1575

Association of Genetic Loci With Glucose Levels in Childhood and Adolescence A Meta-Analysis of Over 6,000 Children. / Barker, A.; Sharp, S. J.; Timpson, N. J.; Bouatia-Naji, N.; Warrington, N. M.; Kanoni, S.; Beilin, L. J.; Brage, S.; Deloukas, P.; Evans, D. M.; Grontved, A.; Hassanali, N.; Lawlor, D. A.; Lecoeur, C.; Loos, R. J. F.; Lye, S. J.; McCarthy, M. I.; Mori, T. A.; Ndiaye, N. C.; Newnham, J. P.; Ntalla, I.; Pennell, C. E.; St Pourcain, B.; Prokopenko, I.; Ring, S. M.; Sattar, N.; Visvikis-Siest, S.; Dedoussis, G. V.; Pahner, L. J.; Froguel, P.; Smith, G. D.; Ekelund, U.; Wareham, N. J.; Langenberg, C.

I: Diabetes, Bind 60, Nr. 6, 2011, s. 1805-1812.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Association of Genetic Loci With Glucose Levels in Childhood and Adolescence A Meta-Analysis of Over 6,000 Children

AU - Barker, A.

AU - Sharp, S. J.

AU - Timpson, N. J.

AU - Bouatia-Naji, N.

AU - Warrington, N. M.

AU - Kanoni, S.

AU - Beilin, L. J.

AU - Brage, S.

AU - Deloukas, P.

AU - Evans, D. M.

AU - Grontved, A.

AU - Hassanali, N.

AU - Lawlor, D. A.

AU - Lecoeur, C.

AU - Loos, R. J. F.

AU - Lye, S. J.

AU - McCarthy, M. I.

AU - Mori, T. A.

AU - Ndiaye, N. C.

AU - Newnham, J. P.

AU - Ntalla, I.

AU - Pennell, C. E.

AU - St Pourcain, B.

AU - Prokopenko, I.

AU - Ring, S. M.

AU - Sattar, N.

AU - Visvikis-Siest, S.

AU - Dedoussis, G. V.

AU - Pahner, L. J.

AU - Froguel, P.

AU - Smith, G. D.

AU - Ekelund, U.

AU - Wareham, N. J.

AU - Langenberg, C.

PY - 2011

Y1 - 2011

N2 - 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 p-cell function, as indicated by homeostasis model assessment of beta-cell function. Analysis using a weighted risk score showed an increase [beta (95% CI)] in fasting glucose level of 0.026 mrnol/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. Diabetes 60:1805-1812, 2011

AB - 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 p-cell function, as indicated by homeostasis model assessment of beta-cell function. Analysis using a weighted risk score showed an increase [beta (95% CI)] in fasting glucose level of 0.026 mrnol/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. Diabetes 60:1805-1812, 2011

U2 - 10.2337/db10-1575

DO - 10.2337/db10-1575

M3 - Journal article

VL - 60

SP - 1805

EP - 1812

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 6

ER -

Barker A, Sharp SJ, Timpson NJ, Bouatia-Naji N, Warrington NM, Kanoni S et al. Association of Genetic Loci With Glucose Levels in Childhood and Adolescence A Meta-Analysis of Over 6,000 Children. Diabetes. 2011;60(6):1805-1812. https://doi.org/10.2337/db10-1575