title: Genome-wide haplotype association mapping in mice identifies a genetic variant in CER1 associated with BMD and fracture in southern Chinese women.
abstract: 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.
authors.affiliation: Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Paul L F
authors.initials: PL
authors.lastname: Tang
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Cheung
authors.forename: Pak C
authors.initials: PC
authors.lastname: Sham
authors.forename: Philip
authors.initials: P
authors.lastname: McClurg
authors.forename: Bob
authors.initials: B
authors.lastname: Lee
authors.forename: Shut-Yan
authors.initials: SY
authors.lastname: Chan
authors.forename: David K
authors.initials: DK
authors.lastname: Smith
authors.forename: Julian A
authors.initials: JA
authors.lastname: Tanner
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Su
authors.forename: Kathryn S E
authors.initials: KS
authors.lastname: Cheah
authors.forename: Annie W C
authors.initials: AW
authors.lastname: Kung
authors.forename: You-Qiang
authors.initials: YQ
authors.lastname: Song
mesh_terms: D000818:Animals; D015519:Bone Density / Q000235:genetics*; D002681:China; D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D050723:Fractures, Bone / Q000235:genetics*; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008815:Mice, Inbred Strains; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C514249:CER1 protein, human; C110586:Cer1 protein, mouse; D016207:Cytokines; D011506:Proteins