The authors state that they have no conflicts of interest.
Article first published online: 29 DEC 2008
Copyright © 2009 ASBMR
Journal of Bone and Mineral Research
Volume 24, Issue 6, pages 1013–1021, June 2009
How to Cite
Tang, P. L., Cheung, C.-L., Sham, P. C., McClurg, P., Lee, B., Chan, S.-Y., Smith, D. K., Tanner, J. A., Su, A. I., Cheah, K. S., Kung, A. W. and Song, Y.-Q. (2009), 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, 24: 1013–1021. doi: 10.1359/jbmr.081258
Published online on December 29, 2008
- Issue published online: 4 DEC 2009
- Article first published online: 29 DEC 2008
- Manuscript Accepted: 23 DEC 2008
- Manuscript Revised: 10 JUL 2008
- Manuscript Received: 1 APR 2008
- southern Chinese women
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.