title: Interactions of osteoporosis candidate genes for age at menarche, age at natural menopause, and maximal height in Han Chinese women.
abstract: OBJECTIVE
  Age at menarche (AAM), age at natural menopause (ANM), and maximal height are closely related to bone mineral densities and osteoporosis. It is still unclear whether osteoporosis susceptibility genes are also associated with AAM, ANM, and maximal height in Chinese women.
  
  
  METHODS
  In this relatively large cross-sectional sample of 722 Han Chinese postmenopausal women, 22 single nucleotide polymorphisms (SNPs) within 12 osteoporosis candidate genes that were identified from genome-wide association studies and replicated in our previous study were studied. The effects of a single gene on the AAM, ANM, and maximal height were investigated by linear regression analysis, whereas the gene-gene interactions were determined by a generalized multifactor dimensionality reduction method.
  
  
  RESULTS
  It was revealed that the major histocompatibility complex (MHC) gene (rs3130340) was associated with ANM even after Bonferroni correction (P = 0.001). A significant gene-gene interaction for ANM involving rs3130340 in MHC, rs1038304 and rs4870044 in estrogen receptor-α gene (ESR1), and a significant three-SNP interaction model (SNP rs2273061 in jagged1, SNP rs6929137 in ESR1, and SNP rs2306033 in low-density lipoprotein receptor-related protein 4) for maximal height were identified. No single or combined effect of tested SNPs on AAM was discovered.
  
  
  CONCLUSIONS
  Our study indicates that osteoporosis susceptibility SNPs, such as ESR1 (rs1038304, rs4870044, rs6929137), MHC (rs3130340), low-density lipoprotein receptor-related protein 4 (rs2306033), and jagged1 (rs2273061), might independently and/or in an interactive manner influence ANM and maximal height. All the SNPs tested had no association with AAM.
authors.affiliation: Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Jiao-tong University School of Medicine, 197 Rui-jin Er Road, Shanghai, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Bin
authors.initials: B
authors.lastname: Cui
authors.forename: Jian-min
authors.initials: JM
authors.lastname: Liu
authors.forename: Min-jia
authors.initials: MJ
authors.lastname: Zhang
authors.forename: Hong-yan
authors.initials: HY
authors.lastname: Zhao
authors.forename: Li-hao
authors.initials: LH
authors.lastname: Sun
authors.forename: Bei
authors.initials: B
authors.lastname: Tao
authors.forename: Lian-zhen
authors.initials: LZ
authors.lastname: Zhang
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D001827:Body Height / Q000235:genetics*; D015519:Bone Density / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D003430:Cross-Sectional Studies; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D000072100:Jagged-1 Protein; D026502:LDL-Receptor Related Proteins / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008572:Menarche / Q000235:genetics*; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000072099:Serrate-Jagged Proteins
chemical_list: D002135:Calcium-Binding Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D026502:LDL-Receptor Related Proteins; C551781:LRP4 protein, human; D008565:Membrane Proteins; D000072099:Serrate-Jagged Proteins