title: Risk Alleles in/near ADCY5, ADRA2A, CDKAL1, CDKN2A/B, GRB10, and TCF7L2 Elevate Plasma Glucose Levels at Birth and in Early Childhood: Results from the FAMILY Study.
abstract: BACKGROUND
  Metabolic abnormalities that lead to type 2 diabetes mellitus begin in early childhood.
  
  
  OBJECTIVE
  We investigate whether common genetic variants identified in adults have an effect on glucose in early life.
  
  
  METHODS
  610 newborns, 463 mothers, and 366 fathers were included in the present study. Plasma glucose and anthropometric characteristics were collected at birth, 3, and 5 years. After quality assessment, 37 SNPs, which have demonstrated an association with fasting plasma glucose at the genome-wide threshold in adults, were studied. Quantitative trait disequilibrium tests and mixed-effects regressions were conducted to estimate an effect of the SNPs on glucose.
  
  
  RESULTS
  Risk alleles for 6 loci increased glucose levels from birth to 5 years of age (ADCY5, ADRA2A, CDKAL1, CDKN2A/B, GRB10, and TCF7L2, 4.85x10-3 ≤ P ≤ 4.60x10-2). Together, these 6 SNPs increase glucose by 0.05 mmol/L for each risk allele in a genotype score (P = 6.33x10-5). None of the associations described in the present study have been reported previously in early childhood.
  
  
  CONCLUSIONS
  Our data support the notion that a subset of loci contributing to plasma glucose variation in adults has an effect at birth and in early life.
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Zahra N
authors.initials: ZN
authors.lastname: Sohani
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.|Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Anand
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Robiou-du-Pont
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Department of Pediatrics, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Morrison
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.|Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sarah D
authors.initials: SD
authors.lastname: McDonald
authors.affiliation: Department of Pediatrics, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Atkinson
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.|Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Koon K
authors.initials: KK
authors.lastname: Teo
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.|Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Meyre
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics; D000328:Adult; D000483:Alleles; D001786:Blood Glucose / Q000032:analysis*; D002675:Child, Preschool; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D051383:GRB10 Adaptor Protein / Q000235:genetics; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics; D012359:tRNA Methyltransferases
chemical_list: C547768:ADRA2A protein, human; D001786:Blood Glucose; C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; C096358:GRB10 protein, human; D018341:Receptors, Adrenergic, alpha-2; D051383:GRB10 Adaptor Protein; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V