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Article: Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass

TitleMeta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass
Authors
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
Citation
Journal Of Bone And Mineral Research, 2007, v. 22 n. 2, p. 173-183 How to Cite?
Abstract
Several 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.
Persistent Identifierhttp://hdl.handle.net/10722/77703
ISSN
2013 Impact Factor: 6.589
ISI Accession Number ID
References

 

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
DC FieldValueLanguage
dc.contributor.authorIoannidis, JPAen_HK
dc.contributor.authorNg, MYen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorZintzaras, Een_HK
dc.contributor.authorLewis, CMen_HK
dc.contributor.authorDeng, HWen_HK
dc.contributor.authorEcons, MJen_HK
dc.contributor.authorKarasik, Den_HK
dc.contributor.authorDevoto, Men_HK
dc.contributor.authorKammerer, CMen_HK
dc.contributor.authorSpector, Ten_HK
dc.contributor.authorAndrew, Ten_HK
dc.contributor.authorCupples, LAen_HK
dc.contributor.authorDuncan, ELen_HK
dc.contributor.authorForoud, Ten_HK
dc.contributor.authorKiel, DPen_HK
dc.contributor.authorKoller, Den_HK
dc.contributor.authorLangdahl, Ben_HK
dc.contributor.authorMitchell, BDen_HK
dc.contributor.authorPeacock, Men_HK
dc.contributor.authorRecker, Ren_HK
dc.contributor.authorShen, Hen_HK
dc.contributor.authorSolChurch, Ken_HK
dc.contributor.authorSpotila, LDen_HK
dc.contributor.authorUitterlinden, AGen_HK
dc.contributor.authorWilson, SGen_HK
dc.contributor.authorKung, AWCen_HK
dc.contributor.authorRalston, SHen_HK
dc.date.accessioned2010-09-06T07:34:48Z-
dc.date.available2010-09-06T07:34:48Z-
dc.date.issued2007en_HK
dc.identifier.citationJournal Of Bone And Mineral Research, 2007, v. 22 n. 2, p. 173-183en_HK
dc.identifier.issn0884-0431en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77703-
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.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Bone and Mineral Research. The Journal's web site is located at http://www.jbmr.org/view/0/index.htmlen_HK
dc.relation.ispartofJournal of Bone and Mineral Researchen_HK
dc.subjectBMDen_HK
dc.subjectGenome scanen_HK
dc.subjectGenome searchen_HK
dc.subjectLinkageen_HK
dc.subjectMeta-analysisen_HK
dc.subjectOsteoporosisen_HK
dc.subject.meshBone Density - geneticsen_HK
dc.subject.meshChromosome Mappingen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGenetic Linkageen_HK
dc.subject.meshGenome, Humanen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMaleen_HK
dc.subject.meshQuantitative Trait Locien_HK
dc.subject.meshSex Factorsen_HK
dc.titleMeta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone massen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0884-0431&volume=22&spage=173&epage=83&date=2007&atitle=Meta-analysis+of+genome-wide+scans+provides+evidence+for+sex-+and+site-specific+regulation+of+bone+massen_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailKung, AWC: awckung@hku.hken_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authorityKung, AWC=rp00368en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1359/jbmr.060806en_HK
dc.identifier.pmid17228994en_HK
dc.identifier.scopuseid_2-s2.0-33846473055en_HK
dc.identifier.hkuros131069en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33846473055&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume22en_HK
dc.identifier.issue2en_HK
dc.identifier.spage173en_HK
dc.identifier.epage183en_HK
dc.identifier.isiWOS:000243668800001-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridIoannidis, JPA=35377033000en_HK
dc.identifier.scopusauthoridNg, MY=8367886400en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridZintzaras, E=6603757989en_HK
dc.identifier.scopusauthoridLewis, CM=7402975073en_HK
dc.identifier.scopusauthoridDeng, HW=34568563000en_HK
dc.identifier.scopusauthoridEcons, MJ=7006283956en_HK
dc.identifier.scopusauthoridKarasik, D=7004384589en_HK
dc.identifier.scopusauthoridDevoto, M=7006410509en_HK
dc.identifier.scopusauthoridKammerer, CM=7005441706en_HK
dc.identifier.scopusauthoridSpector, T=35351391300en_HK
dc.identifier.scopusauthoridAndrew, T=7005877095en_HK
dc.identifier.scopusauthoridCupples, LA=7007090535en_HK
dc.identifier.scopusauthoridDuncan, EL=7006067588en_HK
dc.identifier.scopusauthoridForoud, T=7006590374en_HK
dc.identifier.scopusauthoridKiel, DP=7005526959en_HK
dc.identifier.scopusauthoridKoller, D=35399194400en_HK
dc.identifier.scopusauthoridLangdahl, B=35229491800en_HK
dc.identifier.scopusauthoridMitchell, BD=7401949811en_HK
dc.identifier.scopusauthoridPeacock, M=7101801281en_HK
dc.identifier.scopusauthoridRecker, R=7007086875en_HK
dc.identifier.scopusauthoridShen, H=36126870600en_HK
dc.identifier.scopusauthoridSolChurch, K=6602918031en_HK
dc.identifier.scopusauthoridSpotila, LD=6701453016en_HK
dc.identifier.scopusauthoridUitterlinden, AG=35231615000en_HK
dc.identifier.scopusauthoridWilson, SG=35428868100en_HK
dc.identifier.scopusauthoridKung, AWC=7102322339en_HK
dc.identifier.scopusauthoridRalston, SH=7102615949en_HK

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