Examination of type 2 diabetes loci implicates CDKAL1 as a birth weight gene
- Jianhua Zhao1,
- Mingyao Li2,
- Jonathan P. Bradfield3,
- Kai Wang3,
- Haitao Zhang3,
- Patrick Sleiman3,
- Cecilia E. Kim3,
- Kiran Annaiah3,
- Wendy Glaberson3,
- Joseph T. Glessner3,
- George F. Otieno3,
- Kelly A. Thomas3,
- Maria Garris3,
- Cuiping Hou3,
- Edward C. Frackelton3,
- Rosetta M. Chiavacci3,
- Robert I. Berkowitz4,5,
- Hakon Hakonarson, (hakonarson{at}chop.edu)1,3,6 and
- Struan F.A. Grant (grants{at}chop.edu)1,3,6
- 1Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
- 2Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
- 3Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
- 4Behavioral Health Center and Department of Child and Adolescent Psychiatry, The Children's Hospital of Philadelphia, Philadelphia PA 19104, USA
- 5Center for Weight and Eating Disorders, Department of Psychiatry, University of Pennsylvania, Philadelphia PA 19104, USA
- 6Department of Pediatrics, University of Pennsylvania, Philadelphia PA 19104, USA
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 was demonstrated between low birth weight and single nucleotide polymorphisms (SNPs) at the CDKAL1 and HHEX-IDE loci, regions which have been 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.
Design and Methods: Utilizing data from an ongoing GWA 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, 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 while a perfect surrogate for variation previously implicated for the trait at the same locus only yielded nominally significant association (P=0.01; r2 to 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 shows that the same genetic locus that has been identified as a marker for type 2 diabetes in previous studies also influences birth weight.
Footnotes
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- Received April 6, 2009.
- Accepted June 29, 2009.
- Copyright © American Diabetes Association
