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Article: Meta-analysis of gene-based genome-wide association studies of bone mineral density in Chinese and European subjects
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TitleMeta-analysis of gene-based genome-wide association studies of bone mineral density in Chinese and European subjects
 
AuthorsCheung, CL1
Sham, PC1
Xiao, SM1 1
Bow, CH1
Kung, AWC1 1
 
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
 
CitationOsteoporosis International, 2012, v. 23 n. 1, p. 131-142 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s00198-011-1779-7
 
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.
 
ISSN0937-941X
2012 Impact Factor: 4.039
2012 SCImago Journal Rankings: 1.524
 
DOIhttp://dx.doi.org/10.1007/s00198-011-1779-7
 
PubMed Central IDPMC3249198
 
ISI Accession Number IDWOS:000298645700012
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

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorCheung, CL
 
dc.contributor.authorSham, PC
 
dc.contributor.authorXiao, SM
 
dc.contributor.authorBow, CH
 
dc.contributor.authorKung, AWC
 
dc.date.accessioned2012-02-21T05:43:21Z
 
dc.date.available2012-02-21T05:43:21Z
 
dc.date.issued2012
 
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.
 
dc.description.naturepublished_or_final_version
 
dc.description.otherSpringer Open Choice, 21 Feb 2012
 
dc.identifier.citationOsteoporosis International, 2012, v. 23 n. 1, p. 131-142 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s00198-011-1779-7
 
dc.identifier.citeulike9829113
 
dc.identifier.doihttp://dx.doi.org/10.1007/s00198-011-1779-7
 
dc.identifier.eissn1433-2965
 
dc.identifier.epage142
 
dc.identifier.hkuros192169
 
dc.identifier.isiWOS:000298645700012
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

 
dc.identifier.issn0937-941X
2012 Impact Factor: 4.039
2012 SCImago Journal Rankings: 1.524
 
dc.identifier.issue1
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC3249198
 
dc.identifier.pmid21927923
 
dc.identifier.scopuseid_2-s2.0-84857371203
 
dc.identifier.spage131
 
dc.identifier.urihttp://hdl.handle.net/10722/144935
 
dc.identifier.volume23
 
dc.languageEng
 
dc.publisherSpringer U K. The Journal's web site is located at http://www.springer.com/medicine/orthopedics/journal/198
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofOsteoporosis International
 
dc.relation.referencesReferences in Scopus
 
dc.rightsThe Author(s)
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subjectAssociation study
 
dc.subjectBone mineral density
 
dc.subjectGenetic epidemiology
 
dc.subjectMeta-analysis
 
dc.subjectOsteoporosis
 
dc.titleMeta-analysis of gene-based genome-wide association studies of bone mineral density in Chinese and European subjects
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong