title: Association analysis of ten candidate genes in a large multinational cohort of small for gestational age children and children with idiopathic short stature (NESTEGG study).
abstract: BACKGROUND
  Fetal growth failure has been associated with an increased risk of hypertension, cardiovascular disease and diabetes in adulthood. Exploring the mechanisms underlying this association should improve our understanding of these common adult diseases.
  
  
  METHODS
  We investigated 225 SNPs in 10 genes involved in growth and glucose metabolism (GH1, GHR, IGF1, IGF1R, STAT5A, STAT5B, MAPK1, MAPK3, PPARγ and INS) in 1,437 children from the multinational NESTEGG consortium: 345 patients born small for gestational age who remained short (SGA-S), 288 who showed catch-up growth (SGA-Cu), 410 idiopathic short stature (ISS) and 394 controls. We related genotype to pre- and/or postnatal growth parameters, response to growth hormone (if applicable) and blood pressure.
  
  
  RESULTS
  We found several clinical associations for GH1, GHR, IGF1, IGF1R, PPARγ and MAPK1. One SNP remained significant after Bonferroni's correction: IGF1R SNP rs4966035's minor allele A was significantly more prevalent among SGA and associated with smaller birth length (p = 0.000378) and birth weight (weaker association), independent of gestational age.
  
  
  CONCLUSIONS
  IGF1R SNP rs4966035 is significantly associated with birth length, independent of gestational age. This and other associations suggest that polymorphisms in these genes might partly explain the phenotype of short children born SGA and children with ISS.
authors.affiliation: Division of Endocrinology, Department of Paediatrics, Erasmus MC-Sophia Children's Hospital, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: L C G
authors.initials: LC
authors.lastname: de Graaff
authors.forename: A J L
authors.initials: AJ
authors.lastname: Clark
authors.forename: M
authors.initials: M
authors.lastname: Tauber
authors.forename: M B
authors.initials: MB
authors.lastname: Ranke
authors.forename: L B
authors.initials: LB
authors.lastname: Johnston
authors.forename: J
authors.initials: J
authors.lastname: Caliebe
authors.forename: C
authors.initials: C
authors.lastname: Molinas
authors.forename: N
authors.initials: N
authors.lastname: Amin
authors.forename: C
authors.initials: C
authors.lastname: van Duijn
authors.forename: H
authors.initials: H
authors.lastname: Wollmann
authors.forename: H
authors.initials: H
authors.lastname: Wallaschofski
authors.forename: M O
authors.initials: MO
authors.lastname: Savage
authors.forename: A C S
authors.initials: AC
authors.lastname: Hokken-Koelega
mesh_terms: D001827:Body Height / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004392:Dwarfism / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies; D006130:Growth Disorders / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000254:growth & development; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide