title: Genome-wide association study of bone mineral density in premenopausal European-American women and replication in African-American women.
abstract: BACKGROUND
  Several genome-wide association studies (GWAS) have been performed to identify genes contributing to bone mineral density (BMD), typically in samples of elderly women and men.
  
  
  OBJECTIVE
  The objective of the study was to identify genes contributing to BMD in premenopausal women.
  
  
  METHODS
  GWAS using the Illumina 610Quad array in premenopausal European-American (EA) women and replication of the top 50 single-nucleotide polymorphisms (SNPs) for two BMD measures in African-American (AA) women.
  
  
  METHODS
  Subjects included 1524 premenopausal EA women aged 20-45 yr from 762 sibships and 669 AA premenopausal women aged 20-44 yr from 383 sibships.
  
  
  METHODS
  There were no interventions.
  
  
  METHODS
  BMD was measured at the lumbar spine and femoral neck by dual-energy x-ray absorptiometry. Age- and weight-adjusted BMD values were tested for association with each SNP, with P values determined by permutation.
  
  
  RESULTS
  SNPs in CATSPERB on chromosome 14 provided evidence of association with femoral neck BMD (rs1298989, P = 2.7 x 10(-5); rs1285635, P = 3.0 x 10(-5)) in the EA women, and some supporting evidence was also observed with these SNPs in the AA women (rs1285635, P = 0.003). Genes identified in other BMD GWAS studies, including IBSP and ADAMTS18, were also among the most significant findings in our GWAS.
  
  
  CONCLUSIONS
  Evidence of association to several novel loci was detected in a GWAS of premenopausal EA women, and SNPs in one of these loci also provided supporting evidence in a sample of AA women.
authors.affiliation: Departments of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. dkoller@iupui.edu
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Koller
authors.forename: Shoji
authors.initials: S
authors.lastname: Ichikawa
authors.forename: Dongbing
authors.initials: D
authors.lastname: Lai
authors.forename: Leah R
authors.initials: LR
authors.lastname: Padgett
authors.forename: Kimberly F
authors.initials: KF
authors.lastname: Doheny
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pugh
authors.forename: Justin
authors.initials: J
authors.lastname: Paschall
authors.forename: Siu L
authors.initials: SL
authors.lastname: Hui
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xuei
authors.forename: Munro
authors.initials: M
authors.lastname: Peacock
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Econs
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D000483:Alleles; D044383:Black People; D015519:Bone Density / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D005260:Female; D005272:Femur Neck / Q000033:anatomy & histology; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007196:Indiana / Q000453:epidemiology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017697:Premenopause / Q000235:genetics* / Q000502:physiology*; D011786:Quality Control; D015203:Reproducibility of Results; D013131:Spine / Q000033:anatomy & histology; D044465:White People; D001741:Black or African American