Obesity-susceptibility loci and the tails of the pediatric BMI distribution

Obesity (Silver Spring). 2013 Jun;21(6):1256-60. doi: 10.1002/oby.20319.

Abstract

Objective: To determine whether previously identified adult obesity susceptibility loci were associated uniformly with childhood BMI across the BMI distribution.

Design and methods: Children were recruited through the Children's Hospital of Philadelphia (n = 7,225). Associations between the following loci and BMI were assessed using quantile regression: FTO (rs3751812), MC4R (rs12970134), TMEM18 (rs2867125), BDNF (rs6265), TNNI3K (rs1514175), NRXN3 (rs10146997), SEC16B (rs10913469), and GNPDA2 (rs13130484). BMI z-score (age and gender adjusted) was modeled as the dependent variable, and genotype risk score (sum of risk alleles carried at the 8 loci) was modeled as the independent variable.

Results: Each additional increase in genotype risk score was associated with an increase in BMI z-score at the 5th, 15th, 25th, 50th, 75th, 85th, and 95th BMI z-score percentiles by 0.04 (±0.02, P = 0.08), 0.07 (±0.01, P = 9.58 × 10(-7) ), 0.07 (±0.01, P = 1.10 × 10(-8) ), 0.09 (±0.01, P = 3.13 × 10(-22) ), 0.11 (±0.01, P = 1.35 × 10(-25) ), 0.11 (±0.01, P = 1.98 × 10(-20) ), and 0.06 (±0.01, P = 2.44 × 10(-6) ), respectively. Each additional increase in genotype risk score was associated with an increase in mean BMI z-score by 0.08 (±0.01, P = 4.27 × 10(-20) ).

Conclusion: Obesity risk alleles were more strongly associated with increases in BMI z-score at the upper tail compared to the lower tail of the distribution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Body Mass Index*
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Child
  • Child, Preschool
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • European Continental Ancestry Group / genetics
  • Gene-Environment Interaction
  • Genetic Loci*
  • Genetic Predisposition to Disease*
  • Humans
  • Linear Models
  • Logistic Models
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Obesity / genetics*
  • Philadelphia
  • Polymorphism, Single Nucleotide
  • Proteins / genetics
  • Proteins / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • Proteins
  • SEC16B protein, human
  • neurexin IIIalpha
  • BDNF protein, human
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human