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- Title
Examination of Type 2 Diabetes Loci Implicates CDKAL1 as a Birth Weight Gene.
- Authors
Zhao, Jianhua; Li, Mingyao; Bradfield, Jonathan P.; Wang, Kai; Zhang, Haitao; Sleiman, Patrick; Kim, Cecilia E.; Annaiah, Kiran; Glaberson, Wendy; Glessner, Joseph T.; Otieno, F. George; Thomas, Kelly A.; Garris, Maria; Hou, Cuiping; Frackelton, Edward C.; Chiavacci, Rosetta M.; Berkowitz, Robert I.; Hakonarson, Hakon; Grant, Struan F. A.
- 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 TCFTL2, HHEX-IDE, PPARG, KCNJ11, SLC3OA8, IGF2BP2, CDKAL1, CDKN2A/2B, and JAZF1 with birth weight. RESULTS--Our data show that the minor allele of rs7756992 (P = 8 x 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; re 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. Diabetes 58:2414-2418, 2009
- Subjects
TYPE 2 diabetes; BIRTH weight; LOW birth weight; GENETIC polymorphisms; DISEASE risk factors; BIOMARKERS
- Publication
Diabetes, 2009, Vol 58, Issue 10, p2414
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db09-0506