title: BMI at age 8 years is influenced by the type 2 diabetes susceptibility genes HHEX-IDE and CDKAL1.
abstract: OBJECTIVE
  To determine whether HHEX-IDE and CDKAL1 genes, which are associated with birth weight and susceptibility to type 2 diabetes, continue to influence growth during childhood.
  
  
  METHODS
  BMI, weight, and height at age 8 years expressed as age- and sex-corrected standard deviation scores (SDS) against national reference data and single-nucleotide polymorphism genotyping of HHEX-IDE and CDKAL1 loci were analyzed in 646 prospectively followed children in the German BABYDIAB cohort. All children were singleton full-term births; 386 had mothers with type 1 diabetes, and 260 had fathers with type 1 diabetes and a nondiabetic mother.
  
  
  RESULTS
  Type 2 diabetes risk alleles at the HHEX-IDE locus were associated with reduced BMI-SDS at age 8 years (0.17 SDS per allele; P = 0.004). After stratification for birth weight, both HHEX-IDE and CDKAL1 risk alleles were associated with reduced BMI-SDS (0.45 SDS, P = 0.0002; 0.52 SDS, P = 0.0001) and weight-SDS (0.22 SDS, P = 0.04; 0.56 SDS, P = 0.0002) in children born large for gestational age (>90th percentile) but not children born small or appropriate for gestational age. Within children born large for gestational age, BMI and weight decreased with each additional type 2 diabetes risk allele ( approximately -2 kg per allele; >8 kg overall). Findings were consistent in children of mothers with type 1 diabetes (P < 0.0001) and children of nondiabetic mothers (P = 0.008).
  
  
  CONCLUSIONS
  The type 2 diabetes susceptibility alleles at HHEX-IDE and CDKAL1 loci are associated with low BMI at age 8 years in children who were born large for gestational age.
authors.affiliation: Institut fuer Diabetes forschung der Forschergruppe Diabetes e.V. at Helmholtz Center Munich, Neuherberg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Winkler
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.forename: Lydia
authors.initials: L
authors.lastname: Henneberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Anette-Gabriele
authors.initials: AG
authors.lastname: Ziegler
mesh_terms: D001724:Birth Weight / Q000235:genetics; D015992:Body Mass Index; D002648:Child; D015331:Cohort Studies; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005220:Fathers; D005260:Female; D020022:Genetic Predisposition to Disease; D005858:Germany; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009035:Mothers; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*; D012359:tRNA Methyltransferases
chemical_list: C078492:HHEX protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human
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