Genome-wide haplotype association mapping in mice identifies a genetic variant in CER1 associated with BMD and fracture in 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.
Tang
Paul L F
PL
Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Cheung
Ching-Lung
CL
Sham
Pak C
PC
McClurg
Philip
P
Lee
Bob
B
Chan
Shut-Yan
SY
Smith
David K
DK
Tanner
Julian A
JA
Su
Andrew I
AI
Cheah
Kathryn S E
KS
Kung
Annie W C
AW
Song
You-Qiang
YQ
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
C514249:CER1 protein, human; C110586:Cer1 protein, mouse; D016207:Cytokines; D011506:Proteins