title: Genome-wide association study identified CNP12587 region underlying height variation in Chinese females.
abstract: BACKGROUND
  Human height is a highly heritable trait considered as an important factor for health. There has been limited success in identifying the genetic factors underlying height variation. We aim to identify sequence variants associated with adult height by a genome-wide association study of copy number variants (CNVs) in Chinese.
  
  
  METHODS
  Genome-wide CNV association analyses were conducted in 1,625 unrelated Chinese adults and sex specific subgroup for height variation, respectively. Height was measured with a stadiometer. Affymetrix SNP6.0 genotyping platform was used to identify copy number polymorphisms (CNPs). We constructed a genomic map containing 1,009 CNPs in Chinese individuals and performed a genome-wide association study of CNPs with height.
  
  
  RESULTS
  We detected 10 significant association signals for height (p<0.05) in the whole population, 9 and 11 association signals for Chinese female and male population, respectively. A copy number polymorphism (CNP12587, chr18:54081842-54086942, p = 2.41 × 10(-4)) was found to be significantly associated with height variation in Chinese females even after strict Bonferroni correction (p = 0.048). Confirmatory real time PCR experiments lent further support for CNV validation. Compared to female subjects with two copies of the CNP, carriers of three copies had an average of 8.1% decrease in height. An important candidate gene, ubiquitin-protein ligase NEDD4-like (NEDD4L), was detected at this region, which plays important roles in bone metabolism by binding to bone formation regulators.
  
  
  CONCLUSIONS
  Our findings suggest the important genetic variants underlying height variation in Chinese.
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, College of Medicine, Xi'an Jiaotong University, Xi'an, PR China. cathyzh@mail.xjtu.edu.cn
authors.forename: Yin-Ping
authors.initials: YP
authors.lastname: Zhang
authors.forename: Fei-Yan
authors.initials: FY
authors.lastname: Deng
authors.forename: Tie-Lin
authors.initials: TL
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Xiang-Ding
authors.initials: XD
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Xue-Zheng
authors.initials: XZ
authors.lastname: Zhu
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000328:Adult; D001827:Body Height; D002681:China; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D000075702:Nedd4 Ubiquitin Protein Ligases; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C000618485:Nedd4L protein, human; D044767:Ubiquitin-Protein Ligases