Examination of All Type 2 Diabetes GWAS Loci Reveals HHEX-IDE as a Locus Influencing Pediatric BMI

  1. Struan F.A. Grant1,2,6
  1. 1Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania;
  2. 2Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania;
  3. 3Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania;
  4. 4Behavioral Health Center and Department of Child and Adolescent Psychiatry, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania;
  5. 5Center for Weight and Eating Disorders, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania;
  6. 6Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
  1. Corresponding author: Struan F.A. Grant, grants{at}chop.edu.

Abstract

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

RESEARCH DESIGN AND METHODS Using data from an ongoing GWAS of pediatric BMI in our cohort, we investigated the association of pediatric BMI with 20 single nucleotide polymorphisms at 18 type 2 diabetes 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 = 3,592) and a replication cohort (n = 3,592).

RESULTS Our data show that the major type 2 diabetes 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.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received July 2, 2009.
    • Accepted November 13, 2009.
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  1. Diabetes vol. 59 no. 3 751-755
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