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Genome-wide copy number variation analysis identifies novel candidate loci associated with pediatric obesity

European Journal of Human Geneticsvolume 26pages15881596 (2018) | Download Citation


Obesity is a multifactorial condition that is highly heritable. There have been ~60 susceptibility loci identified, but they only account for a fraction of cases. As copy number variations (CNVs) have been implicated in the etiology of a multitude of human disorders including obesity, here, we investigated the contribution of rare (<1% population frequency) CNVs in pediatric cases of obesity. We genotyped 67 such individuals, including 22 with co-morbid developmental delay and prioritized rare CNVs at known obesity-associated loci, as well as, those impacting genes involved in energy homeostasis or related processes. We identified clinically relevant or potentially clinically relevant CNVs in 15% (10/67) of individuals. Of these, 4% (3/67) had 16p11.2 microdeletions encompassing the known obesity risk gene SH2B1. Notably, we identified two unrelated probands harboring different 6p22.2 microduplications encompassing SCGN, a potential novel candidate gene for obesity. Further, we identified other biologically relevant candidate genes for pediatric obesity including ARID5B, GPR39, PTPRN2, and HNF4G. We found previously reported candidate loci for obesity, and new ones, suggesting CNV analysis may assist in the diagnosis of pediatric obesity.

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The authors would like to thank all the families who participated in this study. Special thanks to the centre for applied genomics for assistance with laboratory and bioinformatics analysis; in particular Bhooma Thiruvahindrapuram and Dr. John Wei. We also thank Drs. Mehdi Zarrei and Sanaa Choufani for helpful comments and suggestions. This project was supported by grants from the Canada Foundation for Innovation, Government of Ontario, the Canadian Institutes of Health Research, and the University of Toronto McLaughlin Centre. SWS holds the GlaxoSmithKline-CIHR Chair in Genome Sciences at The Hospital for Sick Children and the University of Toronto.

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Author notes

  1. These authors contributed equally: Thanuja Selvanayagam, Susan Walker


  1. Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada

    • Thanuja Selvanayagam
    • , Susan Walker
    • , Matthew J. Gazzellone
    • , Barbara Kellam
    • , Cheryl Cytrynbaum
    • , Rosanna Weksberg
    •  & Stephen W. Scherer
  2. The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada

    • Thanuja Selvanayagam
    • , Susan Walker
    • , Matthew J. Gazzellone
    • , Barbara Kellam
    •  & Stephen W. Scherer
  3. Division of Clinical & Metabolic Genetics, The Hospital for Sick Children, Toronto, ON, Canada

    • Cheryl Cytrynbaum
    •  & Rosanna Weksberg
  4. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

    • Cheryl Cytrynbaum
    • , Rosanna Weksberg
    •  & Stephen W. Scherer
  5. Department of Pediatric Laboratory Medicine, Genome Diagnostics, The Hospital for Sick Children, Toronto, ON, Canada

    • Dimitri J. Stavropoulos
  6. Division of Endocrinology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

    • Ping Li
    •  & Jill Hamilton
  7. Division of Pediatric Medicine, Hospital for Sick Children, Toronto, ON, Canada

    • Catherine S. Birken
  8. Department of Pediatrics, University of Toronto, Toronto, ON, Canada

    • Catherine S. Birken
    • , Jill Hamilton
    •  & Rosanna Weksberg
  9. McLaughlin Centre, University of Toronto, Toronto, ON, Canada

    • Stephen W. Scherer


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The authors declare that they have no conflict of interest.

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Correspondence to Rosanna Weksberg or Stephen W. Scherer.

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