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Genome‐Wide Haplotype Association Mapping in Mice Identifies a Genetic Variant in CER1 Associated With BMD and Fracture in Southern Chinese Women
Author(s) -
Tang Paul LF,
Cheung ChingLung,
Sham Pak C,
McClurg Philip,
Lee Bob,
Chan ShutYan,
Smith David K,
Tanner Julian A,
Su Andrew I,
Cheah Kathryn SE,
Kung Annie WC,
Song YouQiang
Publication year - 2009
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.081258
Subject(s) - haplotype , snp , biology , genetics , quantitative trait locus , nonsynonymous substitution , genetic association , genome , osteoporosis , cohort , association mapping , medicine , gene , single nucleotide polymorphism , genotype , endocrinology
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.