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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

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  • Zahra N Sohani
  • Sonia S Anand
  • Sebastien Robiou-du-Pont
  • Katherine M Morrison
  • Sarah D McDonald
  • Stephanie A Atkinson
  • Koon K Teo
  • David Meyre

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.

Suggested Citation

  • Zahra N Sohani & Sonia S Anand & Sebastien Robiou-du-Pont & Katherine M Morrison & Sarah D McDonald & Stephanie A Atkinson & Koon K Teo & David Meyre, 2016. "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, Public Library of Science, vol. 11(4), pages 1-8, April.
    • Handle: RePEc:plo:pone00:0152107
    DOI: 10.1371/journal.pone.0152107
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    1. Steven E. Kahn & Rebecca L. Hull & Kristina M. Utzschneider, 2006. "Mechanisms linking obesity to insulin resistance and type 2 diabetes," Nature, Nature, vol. 444(7121), pages 840-846, December.
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