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Article: Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass
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TitleMeta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass
 
AuthorsIoannidis, JPA18 19 11
Ng, MY9 9
Sham, PC9 2
Zintzaras, E21
Lewis, CM2
Deng, HW8 22 20
Econs, MJ4
Karasik, D10
Devoto, M17
Kammerer, CM16
Spector, T7
Andrew, T7
Cupples, LA15
Duncan, EL3
Foroud, T4
Kiel, DP10
Koller, D4
Langdahl, B23
Mitchell, BD6
Peacock, M4
Recker, R8
Shen, H20
SolChurch, K13
Spotila, LD14
Uitterlinden, AG5
Wilson, SG1
Kung, AWC9
Ralston, SH12 12
 
KeywordsBMD
Genome scan
Genome search
Linkage
Meta-analysis
Osteoporosis
 
Issue Date2007
 
PublisherAmerican Society for Bone and Mineral Research. The Journal's web site is located at http://www.jbmr.org/view/0/index.html
 
CitationJournal Of Bone And Mineral Research, 2007, v. 22 n. 2, p. 173-183 [How to Cite?]
DOI: http://dx.doi.org/10.1359/jbmr.060806
 
AbstractSeveral genome-wide scans have been performed to detect loci that regulate BMD, but these have yielded inconsistent results, with limited replication of linkage peaks in different studies. In an effort to improve statistical power for detection of these loci, we performed a meta-analysis of genome-wide scans in which spine or hip BMD were studied. Evidence was gained to suggest that several chromosomal loci regulate BMD in a site-specific and sex-specific manner. Introduction: BMD is a heritable trait and an important predictor of osteoporotic fracture risk. Several genome-wide scans have been performed in an attempt to detect loci that regulate BMD, but there has been limited replication of linkage peaks between studies. In an attempt to resolve these inconsistencies, we conducted a collaborative meta-analysis of genome-wide linkage scans in which femoral neck BMD (FN-BMD) or lumbar spine BMD (LS-BMD) had been studied. Materials and Methods: Data were accumulated from nine genome-wide scans involving 11,842 subjects. Data were analyzed separately for LS-BMD and FN-BMD and by sex. For each study, genomic bins of 30 cM were defined and ranked according to the maximum LOD score they contained. While various densitometers were used in different studies, the ranking approach that we used means that the results are not confounded by the fact that different measurement devices were used. Significance for high average rank and heterogeneity was obtained through Monte Carlo testing. Results: For LS-BMD, the quantitative trait locus (QTL) with greatest significance was on chromosome 1p13.3-q23.3 (p = 0.004), but this exhibited high heterogeneity and the effect was specific for women. Other significant LS-BMD QTLs were on chromosomes 12q24.31-qter, 3p25.3-p22.1, 11p12-q13.3, and 1q32-q42.3, including one on 18p11-q12.3 that had not been detected by individual studies. For FN-BMD, the strongest QTL was on chromosome 9q31.1-q33.3 (p = 0.002). Other significant QTLs were identified on chromosomes 17p12-q21.33, 14q13.1-q24.1, 9q21.32-q31.1, and 5q14.3-q23.2. There was no correlation in average ranks of bins between men and women and the loci that regulated BMD in men and women and at different sites were largely distinct. Conclusions: This large-scale meta-analysis provided evidence for replication of several QTLs identified in previous studies and also identified a QTL on chromosome 18p11-q12.3, which had not been detected by individual studies. However, despite the large sample size, none of the individual loci identified reached genome-wide significance. © 2007 American Society for Bone and Mineral Research.
 
ISSN0884-0431
2012 Impact Factor: 6.128
2012 SCImago Journal Rankings: 2.523
 
DOIhttp://dx.doi.org/10.1359/jbmr.060806
 
ISI Accession Number IDWOS:000243668800001
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorIoannidis, JPA
 
dc.contributor.authorNg, MY
 
dc.contributor.authorSham, PC
 
dc.contributor.authorZintzaras, E
 
dc.contributor.authorLewis, CM
 
dc.contributor.authorDeng, HW
 
dc.contributor.authorEcons, MJ
 
dc.contributor.authorKarasik, D
 
dc.contributor.authorDevoto, M
 
dc.contributor.authorKammerer, CM
 
dc.contributor.authorSpector, T
 
dc.contributor.authorAndrew, T
 
dc.contributor.authorCupples, LA
 
dc.contributor.authorDuncan, EL
 
dc.contributor.authorForoud, T
 
dc.contributor.authorKiel, DP
 
dc.contributor.authorKoller, D
 
dc.contributor.authorLangdahl, B
 
dc.contributor.authorMitchell, BD
 
dc.contributor.authorPeacock, M
 
dc.contributor.authorRecker, R
 
dc.contributor.authorShen, H
 
dc.contributor.authorSolChurch, K
 
dc.contributor.authorSpotila, LD
 
dc.contributor.authorUitterlinden, AG
 
dc.contributor.authorWilson, SG
 
dc.contributor.authorKung, AWC
 
dc.contributor.authorRalston, SH
 
dc.date.accessioned2010-09-06T07:34:48Z
 
dc.date.available2010-09-06T07:34:48Z
 
dc.date.issued2007
 
dc.description.abstractSeveral genome-wide scans have been performed to detect loci that regulate BMD, but these have yielded inconsistent results, with limited replication of linkage peaks in different studies. In an effort to improve statistical power for detection of these loci, we performed a meta-analysis of genome-wide scans in which spine or hip BMD were studied. Evidence was gained to suggest that several chromosomal loci regulate BMD in a site-specific and sex-specific manner. Introduction: BMD is a heritable trait and an important predictor of osteoporotic fracture risk. Several genome-wide scans have been performed in an attempt to detect loci that regulate BMD, but there has been limited replication of linkage peaks between studies. In an attempt to resolve these inconsistencies, we conducted a collaborative meta-analysis of genome-wide linkage scans in which femoral neck BMD (FN-BMD) or lumbar spine BMD (LS-BMD) had been studied. Materials and Methods: Data were accumulated from nine genome-wide scans involving 11,842 subjects. Data were analyzed separately for LS-BMD and FN-BMD and by sex. For each study, genomic bins of 30 cM were defined and ranked according to the maximum LOD score they contained. While various densitometers were used in different studies, the ranking approach that we used means that the results are not confounded by the fact that different measurement devices were used. Significance for high average rank and heterogeneity was obtained through Monte Carlo testing. Results: For LS-BMD, the quantitative trait locus (QTL) with greatest significance was on chromosome 1p13.3-q23.3 (p = 0.004), but this exhibited high heterogeneity and the effect was specific for women. Other significant LS-BMD QTLs were on chromosomes 12q24.31-qter, 3p25.3-p22.1, 11p12-q13.3, and 1q32-q42.3, including one on 18p11-q12.3 that had not been detected by individual studies. For FN-BMD, the strongest QTL was on chromosome 9q31.1-q33.3 (p = 0.002). Other significant QTLs were identified on chromosomes 17p12-q21.33, 14q13.1-q24.1, 9q21.32-q31.1, and 5q14.3-q23.2. There was no correlation in average ranks of bins between men and women and the loci that regulated BMD in men and women and at different sites were largely distinct. Conclusions: This large-scale meta-analysis provided evidence for replication of several QTLs identified in previous studies and also identified a QTL on chromosome 18p11-q12.3, which had not been detected by individual studies. However, despite the large sample size, none of the individual loci identified reached genome-wide significance. © 2007 American Society for Bone and Mineral Research.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Bone And Mineral Research, 2007, v. 22 n. 2, p. 173-183 [How to Cite?]
DOI: http://dx.doi.org/10.1359/jbmr.060806
 
dc.identifier.doihttp://dx.doi.org/10.1359/jbmr.060806
 
dc.identifier.epage183
 
dc.identifier.hkuros131069
 
dc.identifier.isiWOS:000243668800001
 
dc.identifier.issn0884-0431
2012 Impact Factor: 6.128
2012 SCImago Journal Rankings: 2.523
 
dc.identifier.issue2
 
dc.identifier.openurl
 
dc.identifier.pmid17228994
 
dc.identifier.scopuseid_2-s2.0-33846473055
 
dc.identifier.spage173
 
dc.identifier.urihttp://hdl.handle.net/10722/77703
 
dc.identifier.volume22
 
dc.languageeng
 
dc.publisherAmerican Society for Bone and Mineral Research. The Journal's web site is located at http://www.jbmr.org/view/0/index.html
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Bone and Mineral Research
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshBone Density - genetics
 
dc.subject.meshChromosome Mapping
 
dc.subject.meshFemale
 
dc.subject.meshGenetic Linkage
 
dc.subject.meshGenome, Human
 
dc.subject.meshHumans
 
dc.subject.meshMale
 
dc.subject.meshQuantitative Trait Loci
 
dc.subject.meshSex Factors
 
dc.subjectBMD
 
dc.subjectGenome scan
 
dc.subjectGenome search
 
dc.subjectLinkage
 
dc.subjectMeta-analysis
 
dc.subjectOsteoporosis
 
dc.titleMeta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass
 
dc.typeArticle
 
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Author Affiliations
  1. Sir Charles Gairdner Hospital
  2. King's College London
  3. Churchill Hospital
  4. Indiana University School of Medicine Indianapolis
  5. Erasmus University Medical Center
  6. University of Maryland School of Medicine
  7. St Thomas' Hospital
  8. Creighton University School of Medicine
  9. The University of Hong Kong
  10. Harvard Medical School
  11. Tufts University School of Medicine
  12. Western General Hospital
  13. Nemours
  14. ScienceScribe
  15. Boston University School of Public Health
  16. University of Pittsburgh
  17. CHOP
  18. University of Ioannina, School of Medicine
  19. Foundation for Research and Technology-Hellas
  20. University of Missouri-Kansas City
  21. Panepistimio Thesalias
  22. Hunan Normal University
  23. Ârhus Universitetshospital