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

PLoS One. 2016 Apr 6;11(4):e0152107. doi: 10.1371/journal.pone.0152107. eCollection 2016.

Abstract

Background: Metabolic abnormalities that lead to type 2 diabetes mellitus begin in early childhood.

Objectives: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / genetics
  • Adult
  • Alleles*
  • Blood Glucose / analysis*
  • Child, Preschool
  • Cyclin-Dependent Kinase 5 / genetics
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • GRB10 Adaptor Protein / genetics
  • Genes, p16
  • Genetic Predisposition to Disease*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • Receptors, Adrenergic, alpha-2 / genetics
  • tRNA Methyltransferases

Substances

  • ADRA2A protein, human
  • Blood Glucose
  • CDKN2B protein, human
  • Cyclin-Dependent Kinase Inhibitor p15
  • GRB10 protein, human
  • Receptors, Adrenergic, alpha-2
  • GRB10 Adaptor Protein
  • tRNA Methyltransferases
  • Cyclin-Dependent Kinase 5
  • CDKAL1 protein, human
  • Adenylyl Cyclases
  • adenylyl cyclase type V