Examination of Type 2 Diabetes Loci Implicates CDKAL1 as a Birth Weight Gene

  1. Jianhua Zhao1,
  2. Mingyao Li2,
  3. Jonathan P. Bradfield3,
  4. Kai Wang3,
  5. Haitao Zhang3,
  6. Patrick Sleiman3,
  7. Cecilia E. Kim3,
  8. Kiran Annaiah3,
  9. Wendy Glaberson3,
  10. Joseph T. Glessner3,
  11. F. George Otieno3,
  12. Kelly A. Thomas3,
  13. Maria Garris3,
  14. Cuiping Hou3,
  15. Edward C. Frackelton3,
  16. Rosetta M. Chiavacci3,
  17. Robert I. Berkowitz4,5,
  18. Hakon Hakonarson1,3,6 and
  19. Struan F.A. Grant1,3,6
  1. 1Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania;
  2. 2Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania;
  3. 3Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, 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, Philadelphia, Pennsylvania.
  1. Corresponding authors: Struan F.A. Grant, grants{at}chop.edu, and Hakon Hakonarson, hakonarson{at}chop.edu.

Abstract

OBJECTIVE A number of studies have found that reduced birth weight is associated with type 2 diabetes later in life; however, the underlying mechanism for this correlation remains unresolved. Recently, association has been demonstrated between low birth weight and single nucleotide polymorphisms (SNPs) at the CDKAL1 and HHEX-IDE loci, regions that were previously implicated in the pathogenesis of type 2 diabetes. In order to investigate whether type 2 diabetes risk–conferring alleles associate with low birth weight in our Caucasian childhood cohort, we examined the effects of 20 such loci on this trait.

RESEARCH DESIGN AND METHODS Using data from an ongoing genome-wide association study in our cohort of 5,465 Caucasian children with recorded birth weights, we investigated the association of the previously reported type 2 diabetes–associated variation at 20 loci including TCF7L2, HHEX-IDE, PPARG, KCNJ11, SLC30A8, IGF2BP2, CDKAL1, CDKN2A/2B, and JAZF1 with birth weight.

RESULTS Our data show that the minor allele of rs7756992 (P = 8 × 10−5) at the CDKAL1 locus is strongly associated with lower birth weight, whereas a perfect surrogate for variation previously implicated for the trait at the same locus only yielded nominally significant association (P = 0.01; r2 rs7756992 = 0.677). However, association was not detected with any of the other type 2 diabetes loci studied.

CONCLUSIONS We observe association between lower birth weight and type 2 diabetes risk–conferring alleles at the CDKAL1 locus. Our data show that the same genetic locus that has been identified as a marker for type 2 diabetes in previous studies also influences birth weight.

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 April 6, 2009.
    • Accepted June 29, 2009.
« Previous | Next Article »Table of Contents

This Article

  1. Published online before print July 10, 2009, doi: 10.2337/db09-0506 Diabetes October 2009 vol. 58 no. 10 2414-2418
  1. » Abstract
  2. Full Text
  3. Full Text (PDF)
  4. Online-Only Appendix
  5. All Versions of this Article:
    1. db09-0506v1
    2. 58/10/2414 most recent

Current Issue

  1. November 2009, 58 (11)
    Current Issue
  1. Alert me to new issues of Diabetes