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.
  
  
  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.
authors.affiliation: Medical Research Council Epidemiology Unit, Addenbrooke’s Hospital,Institute of Metabolic Science, Cambridge, U.K.
authors.forename: Adam
authors.initials: A
authors.lastname: Barker
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Sharp
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
authors.forename: Nabila
authors.initials: N
authors.lastname: Bouatia-Naji
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Warrington
authors.forename: Stavroula
authors.initials: S
authors.lastname: Kanoni
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Beilin
authors.forename: Soren
authors.initials: S
authors.lastname: Brage
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.forename: Anders
authors.initials: A
authors.lastname: Grontved
authors.forename: Neelam
authors.initials: N
authors.lastname: Hassanali
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Lawlor
authors.forename: Cecile
authors.initials: C
authors.lastname: Lecoeur
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lye
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Mori
authors.forename: Ndeye Coumba
authors.initials: NC
authors.lastname: Ndiaye
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.forename: Ioanna
authors.initials: I
authors.lastname: Ntalla
authors.forename: Craig E
authors.initials: CE
authors.lastname: Pennell
authors.forename: Beate
authors.initials: B
authors.lastname: St Pourcain
authors.forename: Inga
authors.initials: I
authors.lastname: Prokopenko
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.forename: Sophie
authors.initials: S
authors.lastname: Visvikis-Siest
authors.forename: George V
authors.initials: GV
authors.lastname: Dedoussis
authors.forename: Lyle J
authors.initials: LJ
authors.lastname: Palmer
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: Ulf
authors.initials: U
authors.lastname: Ekelund
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Claudia
authors.initials: C
authors.lastname: Langenberg
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics; D000293:Adolescent; D001786:Blood Glucose / Q000235:genetics*; D002648:Child; D056931:Cryptochromes / Q000235:genetics; D004268:DNA-Binding Proteins; D005215:Fasting / Q000097:blood*; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D000081410:Germinal Center Kinases; D051273:Glucose Transporter Type 2 / Q000235:genetics; D005952:Glucose-6-Phosphatase / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D001786:Blood Glucose; C538966:CRY2 protein, human; D056931:Cryptochromes; D004268:DNA-Binding Proteins; C512851:GLIS3 protein, human; D000081410:Germinal Center Kinases; D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; D012097:Repressor Proteins; C495680:SLC2A2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D017346:Protein Serine-Threonine Kinases; D005952:Glucose-6-Phosphatase; C492194:G6PC2 protein, human; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V