Examination of all type 2 diabetes GWAS loci reveals HHEX-IDE as a locus influencing pediatric BMI

  1. Jianhua Zhao1,
  2. Jonathan P. Bradfield2,
  3. Haitao Zhang2,
  4. Kiran Annaiah2,
  5. Kai Wang2,
  6. Cecilia E. Kim2,
  7. Joseph T. Glessner2,
  8. Edward C. Frackelton2,
  9. F. George Otieno2,
  10. James Doran2,
  11. Kelly A. Thomas2,
  12. Maria Garris2,
  13. Cuiping Hou2,
  14. Rosetta M. Chiavacci2,
  15. Mingyao Li3,
  16. Robert I. Berkowitz4,5,
  17. Hakon Hakonarson1,2,6 and
  18. Struan F.A. Grant (grants{at},2,6
  1. 1Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
  2. 2Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
  3. 3Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
  4. 4Behavioral Health Center and Department of Child and Adolescent Psychiatry, The Children's Hospital of Philadelphia, Philadelphia PA 19104, USA
  5. 5Center for Weight and Eating Disorders, Department of Psychiatry, University of Pennsylvania, Philadelphia PA 19104, USA
  6. 6Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA


    Objective: A number of studies have found that body mass index (BMI) in early life influences the risk of developing type 2 diabetes (T2D) later in life. Our goal was to investigate if any T2D variants uncovered through genome wide association studies (GWAS) impact BMI in childhood.

    Design and Methods: Utilizing data from an ongoing GWAS of pediatric BMI in our cohort, we investigated the association of pediatric BMI with 20 SNPs at 18 T2D loci uncovered through GWAS, consisting of ADAMTS9, CDC123-CAMK1D, CDKAL1, CDKN2A/B, EXT2, FTO, HHEX-IDE, IGF2BP2, the intragenic region on 11p12, JAZF1, KCNQ1, LOC387761, MTNR1B, NOTCH2, SLC30A8, TCF7L2, THADA and TSPAN8-LGR5. We randomly partitioned our cohort exactly in half in order to have a ‘discovery’ cohort (n=3592) and a ‘replication’ cohort (n=3592).

    Results: Our data show that the major, T2D-risk conferring G allele of rs7923837 at the HHEX-IDE locus was associated with higher pediatric BMI in both the discovery (P=0.0013; and survived correction for 20 tests) and replication (P=0.023) sets (combined P=1.01×10−4). Association was not detected with any other known type 2 diabetes loci uncovered to date through GWAS except for the well established FTO.

    Conclusions: Our data show that the same genetic HHEX-IDE variant which is associated with type 2 diabetes from previous studies also influences pediatric BMI.


      • Received July 2, 2009.
      • Accepted November 13, 2009.

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