Genome-wide haplotype association mapping in mice identifies a genetic variant in CER1 associated with BMD and fracture in southern Chinese women

J Bone Miner Res. 2009 Jun;24(6):1013-21. doi: 10.1359/jbmr.081258.


BMD is a heritable trait and risk indicator for osteoporosis. In this study, we used a genome-wide haplotype association mapping (HAM) approach to identify a haplotype block within Cer1 that partitions inbred mice strains into high and low BMD groups. A cohort of 1083 high and low BMD human subjects were studied, and a nonsynonymous SNP (rs3747532) in human CER1 was identified to be associated with increased risk of both low BMD in premenopausal women (OR: 2.2; 95% CI: 1.0-4.6; p < 0.05) and increased risk of vertebral fractures (OR: 1.82, p = 0.025) in the postmenopausal cohort. We also showed that Cer1 is expressed in mouse bone and growth plate by RT-PCR, immunohistochemistry, and in situ hybridization, consistent with polymorphisms potentially influencing BMD. Our successful identification of an association with CER1 in humans together with our mouse study suggests that CER1 may play a role in the development of bone or its metabolism. Our study highlights the use of publicly available databases for rapidly surveying the genome for quantitative trait loci.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Density / genetics*
  • China
  • Cohort Studies
  • Cytokines / genetics*
  • Female
  • Fractures, Bone / genetics*
  • Genome-Wide Association Study*
  • Haplotypes*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Mice, Inbred Strains
  • Polymorphism, Single Nucleotide
  • Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction


  • CER1 protein, human
  • Cer1 protein, mouse
  • Cytokines
  • Proteins