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

BackgroundMetabolic abnormalities that lead to type 2 diabetes mellitus begin in early childhood.ObjectivesWe investigate whether common genetic variants identified in adults have an effect on glucose in early life.Methods610 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.ResultsRisk 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.ConclusionOur 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.