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Article: Meta-analysis of gene-based genome-wide association studies of bone mineral density in Chinese and European subjects

TitleMeta-analysis of gene-based genome-wide association studies of bone mineral density in Chinese and European subjects
Authors
KeywordsAssociation study
Bone mineral density
Genetic epidemiology
Meta-analysis
Osteoporosis
Issue Date2012
PublisherSpringer U K. The Journal's web site is located at http://www.springer.com/medicine/orthopedics/journal/198
Citation
Osteoporosis International, 2012, v. 23 n. 1, p. 131-142 How to Cite?
AbstractSummary Gene-based association approach could be regarded as a complementary analysis to the single SNP association analysis. We meta-analyzed the findings from the gene-based association approach using the genome-wide association studies (GWAS) data from Chinese and European subjects, confirmed several well established bone mineral density (BMD) genes, and suggested several novel BMD genes. Introduction The introduction of GWAS has greatly increased the number of genes that are known to be associated with common diseases. Nonetheless, such a single SNP GWAS has a lower power to detect genes with multiple causal variants. We aimed to assess the association of each gene with BMD variation at the spine and hip using gene-based GWAS approach. Methods We studied 778 Hong Kong Southern Chinese (HKSC) women and 5,858 Northern Europeans (dCG); age, sex, and weight were adjusted in the model. The main outcome measure was BMD at the spine and hip. Results Nine genes showed suggestive p value in HKSC, while 4 and 17 genes showed significant and suggestive p values respectively in dCG. Meta-analysis using weighted Z-transformed test confirmed several known BMD genes and suggested some novel ones at 1q21.3, 9q22, 9q33.2, 20p13, and 20q12. Top BMD genes were significantly associated with connective tissue, skeletal, and muscular system development and function (p<0.05). Gene network inference revealed that a large number of these genes were significantly connected with each other to form a functional gene network, and several signaling pathways were strongly connected with these gene networks. Conclusion Our gene-based GWAS confirmed several BMD genes and suggested several novel BMD genes. Genetic contribution to BMD variation may operate through multiple genes identified in this study in functional gene networks. This finding may be useful in identifying and prioritizing candidate genes/loci for further study. © International Osteoporosis Foundation and National Osteoporosis Foundation 2011.
Persistent Identifierhttp://hdl.handle.net/10722/144935
ISSN
2015 Impact Factor: 3.445
2015 SCImago Journal Rankings: 1.460
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of the Hong Kong Government
Osteoporosis Research Fund
University of Hong Kong
Funding Information:

This work was supported by the Research Grant Council of the Hong Kong Government, The Osteoporosis Research Fund, and Matching Grant of the University of Hong Kong

References

 

DC FieldValueLanguage
dc.contributor.authorCheung, CLen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorXiao, SMen_HK
dc.contributor.authorBow, CHen_HK
dc.contributor.authorKung, AWCen_HK
dc.date.accessioned2012-02-21T05:43:21Z-
dc.date.available2012-02-21T05:43:21Z-
dc.date.issued2012en_HK
dc.identifier.citationOsteoporosis International, 2012, v. 23 n. 1, p. 131-142en_HK
dc.identifier.issn0937-941Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/144935-
dc.description.abstractSummary Gene-based association approach could be regarded as a complementary analysis to the single SNP association analysis. We meta-analyzed the findings from the gene-based association approach using the genome-wide association studies (GWAS) data from Chinese and European subjects, confirmed several well established bone mineral density (BMD) genes, and suggested several novel BMD genes. Introduction The introduction of GWAS has greatly increased the number of genes that are known to be associated with common diseases. Nonetheless, such a single SNP GWAS has a lower power to detect genes with multiple causal variants. We aimed to assess the association of each gene with BMD variation at the spine and hip using gene-based GWAS approach. Methods We studied 778 Hong Kong Southern Chinese (HKSC) women and 5,858 Northern Europeans (dCG); age, sex, and weight were adjusted in the model. The main outcome measure was BMD at the spine and hip. Results Nine genes showed suggestive p value in HKSC, while 4 and 17 genes showed significant and suggestive p values respectively in dCG. Meta-analysis using weighted Z-transformed test confirmed several known BMD genes and suggested some novel ones at 1q21.3, 9q22, 9q33.2, 20p13, and 20q12. Top BMD genes were significantly associated with connective tissue, skeletal, and muscular system development and function (p<0.05). Gene network inference revealed that a large number of these genes were significantly connected with each other to form a functional gene network, and several signaling pathways were strongly connected with these gene networks. Conclusion Our gene-based GWAS confirmed several BMD genes and suggested several novel BMD genes. Genetic contribution to BMD variation may operate through multiple genes identified in this study in functional gene networks. This finding may be useful in identifying and prioritizing candidate genes/loci for further study. © International Osteoporosis Foundation and National Osteoporosis Foundation 2011.en_HK
dc.languageengen_US
dc.publisherSpringer U K. The Journal's web site is located at http://www.springer.com/medicine/orthopedics/journal/198en_HK
dc.relation.ispartofOsteoporosis Internationalen_HK
dc.rightsThe Author(s)en_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong Licenseen_US
dc.subjectAssociation studyen_HK
dc.subjectBone mineral densityen_HK
dc.subjectGenetic epidemiologyen_HK
dc.subjectMeta-analysisen_HK
dc.subjectOsteoporosisen_HK
dc.titleMeta-analysis of gene-based genome-wide association studies of bone mineral density in Chinese and European subjectsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4551/resserv?sid=springerlink&genre=article&atitle=Meta-analysis of gene-based genome-wide association studies of bone mineral density in Chinese and European subjects&title=Osteoporosis International&issn=0937941X&date=2012-01-01&volume=23&issue=1& spage=131&authors=C.-L. Cheung, P.-C. Sham, S.-M. Xiao, <i>et al.</i>en_US
dc.identifier.emailCheung, CL: lung1212@hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailKung, AWC: awckung@hku.hken_HK
dc.identifier.authorityCheung, CL=rp01749en_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authorityKung, AWC=rp00368en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1007/s00198-011-1779-7en_HK
dc.identifier.pmid21927923-
dc.identifier.pmcidPMC3249198-
dc.identifier.scopuseid_2-s2.0-84857371203en_HK
dc.identifier.hkuros192169-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84857371203&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume23en_HK
dc.identifier.issue1en_HK
dc.identifier.spage131en_HK
dc.identifier.epage142en_HK
dc.identifier.eissn1433-2965en_US
dc.identifier.isiWOS:000298645700012-
dc.publisher.placeUnited Kingdomen_HK
dc.description.otherSpringer Open Choice, 21 Feb 2012en_US
dc.identifier.scopusauthoridCheung, CL=14520953400en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridXiao, SM=7402022586en_HK
dc.identifier.scopusauthoridBow, CH=36055977600en_HK
dc.identifier.scopusauthoridKung, AWC=7102322339en_HK
dc.identifier.citeulike9829113-

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