title: Association Study of GWAS-Derived Loci with Height in Brazilian Children: Importance of MAP3K3, MMP24 and IGF1R Polymorphisms for Height Variation.
abstract: OBJECTIVE
  The single nucleotide polymorphisms (SNPs) rs2282978 (CDK6), rs2425019 (MMP24), rs8081612 (MAP3K3), rs2871865 (IGF1R) and rs3782415 (SOCS2) were among the SNPs most strongly associated with height in a meta-analysis of 47 genome-wide association studies (GWAS) involving 114,223 adults from six ethnic groups. The present study aimed to examine associations between these SNPs and height in Brazilian children.
  
  
  METHODS
  Cross-sectional heights of 1,008 healthy unrelated 4.4- to 9.7-year-old children were evaluated. All genotypes were determined by allele-specific polymerase chain reactions. Height standard deviation scores (SDS) were generated for this population and regressed on allele counts. Linear regressions were performed to estimate the effect of individual SNPs or a polygenic allelic score on height.
  
  
  RESULTS
  The T allele of rs8081612 (MAP3K3), the C allele of rs2871865 (IGF1R) and the G allele of rs2425019 (MMP24) were significantly associated with a 0.091-SDS greater height (95% CI 0.089-0.093, p = 0.001) by polygenic analysis. The mean height SDS difference between children with 2 'tall' alleles and children with 4 'tall' alleles was 0.24 SDS (95% CI 0.05-0.43, p = 0.01). The observed allelic effect is consistent with that found in previous GWAS.
  
  
  CONCLUSIONS
  Polymorphisms in MAP3K3, MMP24 and IGF1R act additively on height in children of an admixed population. These results demonstrate the importance of these loci for children's height.
authors: Laboratorio de Farmacogenetica, FARMAGEN, Unidade de Farmacologia Clx00ED;nica, Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Fortaleza, Brazil.
authors: Eveline Gadelha Pereira
authors: EG
authors: Fontenele
authors: Maria Elisabete Amaral de
authors: ME
authors: Moraes
authors: Catarina Brasil
authors: CB
authors: d'Alva
authors: Daniel Pascoalino
authors: DP
authors: Pinheiro
authors: Sara Aguiar Sales Pinheiro
authors: SA
authors: Landim
authors: Fernando Antonio de Sousa
authors: FA
authors: Barros
authors: Ericka Barbosa
authors: EB
authors: Trarbach
authors: Berenice Bilharinho de
authors: BB
authors: Mendonca
authors: Alexander Augusto Lima
authors: AA
authors: Jorge
mesh_terms: D000483:Alleles; D001827:Body Height / Q000235:genetics*; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D048748:MAP Kinase Kinase Kinase 3 / Q000235:genetics*; D008297:Male; D053504:Matrix Metalloproteinases, Membrane-Associated / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics*
chemical_list: C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; D017526:Receptor, IGF Type 1; D048748:MAP Kinase Kinase Kinase 3; C482625:MAP3K3 protein, human; C492243:MMP24 protein, human; D053504:Matrix Metalloproteinases, Membrane-Associated