title: Examination of type 2 diabetes loci implicates CDKAL1 as a birth weight gene.
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.
  
  
  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 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; r(2) 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.
authors: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors: Jianhua
authors: J
authors: Zhao
authors: Mingyao
authors: M
authors: Li
authors: Jonathan P
authors: JP
authors: Bradfield
authors: Kai
authors: K
authors: Wang
authors: Haitao
authors: H
authors: Zhang
authors: Patrick
authors: P
authors: Sleiman
authors: Cecilia E
authors: CE
authors: Kim
authors: Kiran
authors: K
authors: Annaiah
authors: Wendy
authors: W
authors: Glaberson
authors: Joseph T
authors: JT
authors: Glessner
authors: F George
authors: FG
authors: Otieno
authors: Kelly A
authors: KA
authors: Thomas
authors: Maria
authors: M
authors: Garris
authors: Cuiping
authors: C
authors: Hou
authors: Edward C
authors: EC
authors: Frackelton
authors: Rosetta M
authors: RM
authors: Chiavacci
authors: Robert I
authors: RI
authors: Berkowitz
authors: Hakon
authors: H
authors: Hakonarson
authors: Struan F A
authors: SF
authors: Grant
mesh_terms: D001724:Birth Weight / Q000235:genetics*; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D015143:Philadelphia; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D012359:tRNA Methyltransferases
chemical_list: D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human