Conference Paper: Genome-wide Haplotype Association mapping in mice identifies a genetic variant in CER1 associated with bone mineral density and fracture in southern Chinese women

TitleGenome-wide Haplotype Association mapping in mice identifies a genetic variant in CER1 associated with bone mineral density and fracture in southern Chinese women
Authors
KeywordsGenetic disease
BMD
cer1
Genome-wide Haplotype Association Mapping (HAM)
Issue Date2009
Citation
The 59th Annual Meeting of The American Society of Human Genetics (ASHG 2009), Honolulu, HI., 20-24 October 2009. How to Cite?
AbstractINTRODUCTION: Osteoporosis is characterized by a decrease in bone mass, deterioration of bone tissue, impaired bone strength and increased fracture risk. It is a medically, socially, and economically important disease, especially among the aging population. Bone Mass Density (BMD) is a quantitative index of osteoporosis. Acquisition of bone mineral is a complex process involving genetics and environmental factors. METHODS: A genome-wide Haplotype Association Mapping (HAM) approach was performed by using inbred mice strains which had been genotyped and phenotyped in the Mouse Phenome Project. In HAM, a dense SNPs map was first partitioned into blocks of three SNPs with an average length of 1Mb. Modified F-statistics were calculated for the whole genome to test if blocks exist where the haplotypes can partition inbred strains into high and low BMD groups. In this study, the candidate gene Cerberus 1 (Cer1) suggested from HAM analysis was eventually tested by a human case-control cohort of 1,083 subjects. RESULTS AND CONCLUSION: In this study, we used a 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 non-synonymous SNP (rs3747532) in human CER1 was identified to be associated with increased risk of both low BMD in premenopausal women (OR 2.2; 95% confidence interval: 1.0 - 4.6; p < 0.05) and increased risk of vertebral fractures (OR 1.82, p=0.025) in the post-menopausal 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 bone mineral density. 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.
Persistent Identifierhttp://hdl.handle.net/10722/129617

 

DC FieldValueLanguage
dc.contributor.authorSong, Yen_US
dc.contributor.authorTang, LFen_US
dc.contributor.authorCheung, CLen_US
dc.contributor.authorSham, PCen_US
dc.contributor.authorMcClurg, Pen_US
dc.contributor.authorSmith, DKen_US
dc.contributor.authorTanner, JAen_US
dc.contributor.authorSu, AIen_US
dc.contributor.authorCheah, KSEen_US
dc.contributor.authorKung, AWCen_US
dc.date.accessioned2010-12-23T08:40:07Z-
dc.date.available2010-12-23T08:40:07Z-
dc.date.issued2009en_US
dc.identifier.citationThe 59th Annual Meeting of The American Society of Human Genetics (ASHG 2009), Honolulu, HI., 20-24 October 2009.en_US
dc.identifier.urihttp://hdl.handle.net/10722/129617-
dc.description.abstractINTRODUCTION: Osteoporosis is characterized by a decrease in bone mass, deterioration of bone tissue, impaired bone strength and increased fracture risk. It is a medically, socially, and economically important disease, especially among the aging population. Bone Mass Density (BMD) is a quantitative index of osteoporosis. Acquisition of bone mineral is a complex process involving genetics and environmental factors. METHODS: A genome-wide Haplotype Association Mapping (HAM) approach was performed by using inbred mice strains which had been genotyped and phenotyped in the Mouse Phenome Project. In HAM, a dense SNPs map was first partitioned into blocks of three SNPs with an average length of 1Mb. Modified F-statistics were calculated for the whole genome to test if blocks exist where the haplotypes can partition inbred strains into high and low BMD groups. In this study, the candidate gene Cerberus 1 (Cer1) suggested from HAM analysis was eventually tested by a human case-control cohort of 1,083 subjects. RESULTS AND CONCLUSION: In this study, we used a 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 non-synonymous SNP (rs3747532) in human CER1 was identified to be associated with increased risk of both low BMD in premenopausal women (OR 2.2; 95% confidence interval: 1.0 - 4.6; p < 0.05) and increased risk of vertebral fractures (OR 1.82, p=0.025) in the post-menopausal 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 bone mineral density. 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.-
dc.languageengen_US
dc.relation.ispartofAnnual Meeting of the American Society of Human Genetics, ASHG 2009-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectGenetic disease-
dc.subjectBMD-
dc.subjectcer1-
dc.subjectGenome-wide Haplotype Association Mapping (HAM)-
dc.titleGenome-wide Haplotype Association mapping in mice identifies a genetic variant in CER1 associated with bone mineral density and fracture in southern Chinese womenen_US
dc.typeConference_Paperen_US
dc.identifier.emailSong, Y: songy@hku.hken_US
dc.identifier.emailTang, LF: tanglingfung@gmail.comen_US
dc.identifier.emailCheung, CL: lung1212@hku.hken_US
dc.identifier.emailSham, PC: pcsham@hku.hken_US
dc.identifier.emailSmith, DK: dsmith@hku.hken_US
dc.identifier.emailTanner, JA: jatanner@hku.hken_US
dc.identifier.emailCheah, KSE: hrmbdkc@hku.hken_US
dc.identifier.emailKung, AWC: awckung@hku.hk-
dc.identifier.authoritySong, Y=rp00488en_US
dc.identifier.authoritySham, PC=rp00459en_US
dc.identifier.authorityTanner, JA=rp00495en_US
dc.identifier.authorityCheah, KSE=rp00342en_US
dc.identifier.authorityKung, AWC=rp00368en_US
dc.description.naturepostprint-
dc.identifier.hkuros178551en_US
dc.description.otherThe 59th Annual Meeting of The American Society of Human Genetics (ASHG), Honolulu, HI., 20-24 October 2009.-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats