Role of BMI-Associated Loci Identified in GWAS Meta-Analyses in the Context of Common Childhood Obesity in European Americans

Authors

  • Jianhua Zhao,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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  • Jonathan P. Bradfield,

    1. Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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  • Haitao Zhang,

    1. Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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  • Patrick M. Sleiman,

    1. Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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  • Cecilia E. Kim,

    1. Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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  • Joseph T. Glessner,

    1. Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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  • Sandra Deliard,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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  • Kelly A. Thomas,

    1. Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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  • Edward C. Frackelton,

    1. Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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  • Mingyao Li,

    1. Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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  • Rosetta M. Chiavacci,

    1. Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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  • Robert I. Berkowitz,

    1. Behavioral Health Center and Department of Child and Adolescent Psychiatry, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    2. Center for Weight and Eating Disorders, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    3. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
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  • Hakon Hakonarson,

    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    2. Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    3. Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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  • Struan F.A. Grant

    Corresponding author
    1. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    2. Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    3. Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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  • The first two authors contributed equally to the work.

(grants@chop.edu)

Abstract

Obesity is a serious health concern for children and adolescents, particularly in Western societies, where its incidence is now considered to have reached epidemic proportions. A number of genetic determinants of adult BMI have already been established through genome wide association studies (GWAS), most recently from the GIANT meta-analysis of such datasets combined. In this current study of European Americans, we examined the 32 loci detected in that GIANT study in the context of common childhood obesity within a cohort of 1,097 cases (defined as BMI ≥95th percentile), together with 2,760 lean controls (defined as BMI <50th percentile), aged between 2 and 18 years old. Nine of these single-nucleotide polymorphims (SNPs) yielded at least nominal evidence for association with common childhood obesity, namely at the FTO, TMEM18, NRXN3, MC4R, SEC16B, GNPDA2, TNNI3K, QPCTL, and BDNF loci. However, overall 28 of the 32 loci showed directionally consistent effects to that of the adult BMI meta-analysis. We conclude that among the 32 loci that have been reported to associate with adult BMI in the largest meta-analysis of BMI to date, at least nine also contribute to the determination of common obesity in childhood in European Americans, as demonstrated by their associations in our pediatric cohort.

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