BMD-Associated Variation at the Osterix Locus Is Correlated With Childhood Obesity in Females

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, The Children's Hospital of Philadelphia Research Institute, 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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  • Haitao Zhang,

    1. Center for Applied Genomics, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, USA
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  • Frank D. Mentch,

    1. Center for Applied Genomics, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, USA
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  • Kai Wang,

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

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

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

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

    1. Center for Applied Genomics, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, USA
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  • Rosetta M. Chiavacci,

    1. Center for Applied Genomics, The Children's Hospital of Philadelphia Research Institute, 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
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  • Babette S. Zemel,

    1. Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    2. Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, 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, The Children's Hospital of Philadelphia Research Institute, 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, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, USA
    3. Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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(grants@chop.edu)

Abstract

Recent genome wide association studies (GWAS) have revealed a number of genetic variants robustly associated with bone mineral density (BMD) and/or osteoporosis. Evidence from epidemiological and clinical studies has shown an association between BMD and BMI, presumably as a consequence of bone loading. We investigated the 23 previously published BMD GWAS-derived loci in the context of childhood obesity by leveraging our existing genome-wide genotyped European American cohort of 1,106 obese children (BMI ≥95th percentile) and 5,997 controls (BMI <95th percentile). Evidence of association was only observed at one locus, namely Osterix (SP7), with the G allele of rs2016266 being significantly over-represented among childhood obesity cases (P = 2.85 × 10−3). When restricting these analyses to each gender, we observed strong association between rs2016266 and childhood obesity in females (477 cases and 2,867 controls; P = 3.56 × 10−4), which survived adjustment for all tests applied. However, no evidence of association was observed among males. Interestingly, Osterix is the only GWAS locus uncovered to date that has also been previously implicated in the determination of BMD in childhood. In conclusion, these findings indicate that a well established variant at the Osterix locus associated with increased BMD is also associated with childhood obesity primarily in females.

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