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

Authors

  • Jonathan A. Mitchell,

    1. Center for Genetics and Complex Traits, Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, USA
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    • Disclosure: No conflicts of interest to declare.

  • Hakon Hakonarson,

    1. Center for Applied Genomics, Abramson Research Center, Children's Hospital of Philadelphia, Pennsylvania, Philadelphia, USA
    2. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    3. Institute of Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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  • Timothy R. Rebbeck,

    1. Center for Genetics and Complex Traits, Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, USA
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  • Struan F.A. Grant

    1. Center for Applied Genomics, Abramson Research Center, Children's Hospital of Philadelphia, Pennsylvania, Philadelphia, USA
    2. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    3. Institute of Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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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.

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