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Article: Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

TitleGenome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture
Authors
Estrada, KStyrkarsdottir, UEvangelou, EHsu, YHDuncan, ELNtzani, EEOei, LAlbagha, OMEAmin, NKemp, JPKoller, DLLi, GLiu, CTMinster, RLMoayyeri, AVandenput, LWillner, DXiao, SMYergesArmstrong, LMZheng, HFAlonso, NEriksson, JKammerer, CMKaptoge, SKLeo, PJThorleifsson, GWilson, SGWilson, JFAalto, VAlen, MAragaki, AKAspelund, TCenter, JRDailiana, ZDuggan, DJGarcia, MGarciaGiralt, NGiroux, SHallmans, GHocking, LJHusted, LBJameson, KAKhusainova, RKim, GSKooperberg, CKoromila, TKruk, MLaaksonen, MLacroix, AZLee, SHLeung, PCLewis, JRMasi, LMencejBedrac, SNguyen, TVNogues, XPatel, MSPrezelj, JRose, LMScollen, SSiggeirsdottir, KSmith, AVSvensson, OTrompet, STrummer, OVan Schoor, NMWoo, JZhu, KBalcells, SBrandi, MLBuckley, BMCheng, SChristiansen, CCooper, CDedoussis, GFord, IFrost, MGoltzman, DGonzálezMacías, JKähönen, MKarlsson, MKhusnutdinova, EKoh, JMKollia, PLangdahl, BLLeslie, WDLips, PLjunggren, OLorenc, RSMarc, JMellström, DObermayerPietsch, BOlmos, JMPetterssonKymmer, UReid, DMRiancho, JARidker, PMRousseau, FLagboom, PESTang, NLSUrreizti, RVan Hul, WViikari, JZarrabeitia, MTAulchenko, YSCastanoBetancourt, MGrundberg, EHerrera, LIngvarsson, TJohannsdottir, HKwan, TLi, RLuben, RMedinaGómez, CTh Palsson, SReppe, SRotter, JISigurdsson, GVan Meurs, JBJVerlaan, DWilliams, FMKWood, ARZhou, YGautvik, KMPastinen, TRaychaudhuri, SCauley, JAChasman, DIClark, GRCummings, SRDanoy, PDennison, EMEastell, REisman, JAGudnason, VHofman, AJackson, RDJones, GJukema, JWKhaw, KTLehtimäki, TLiu, YLorentzon, MMccloskey, EMitchell, BDNandakumar, KNicholson, GCOostra, BAPeacock, MPols, HAPPrince, RLRaitakari, OReid, IRRobbins, JSambrook, PNSham, PCShuldiner, ARTylavsky, FAVan Duijn, CMWareham, NJCupples, LAEcons, MJEvans, DMHarris, TBKung, AWCPsaty, BMReeve, JSpector, TDStreeten, EAZillikens, MCThorsteinsdottir, UOhlsson, CKarasik, DRichards, JBBrown, MAStefansson, KUitterlinden, AGRalston, SHIoannidis, JPAKiel, DPRivadeneira, F
Issue Date2012
PublisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.com
Citation
Nature Genetics, 2012, v. 44 n. 5, p. 491-501 How to Cite?
AbstractBone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10 -8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10 -4, Bonferroni corrected), of which six reached P < 5 × 10 -8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility. © 2012 Nature America, Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/175990
ISSN
2023 Impact Factor: 31.7
2023 SCImago Journal Rankings: 17.300
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorEstrada, Ken_US
dc.contributor.authorStyrkarsdottir, Uen_US
dc.contributor.authorEvangelou, Een_US
dc.contributor.authorHsu, YHen_US
dc.contributor.authorDuncan, ELen_US
dc.contributor.authorNtzani, EEen_US
dc.contributor.authorOei, Len_US
dc.contributor.authorAlbagha, OMEen_US
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dc.contributor.authorCauley, JAen_US
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dc.contributor.authorEastell, Ren_US
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dc.contributor.authorHofman, Aen_US
dc.contributor.authorJackson, RDen_US
dc.contributor.authorJones, Gen_US
dc.contributor.authorJukema, JWen_US
dc.contributor.authorKhaw, KTen_US
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dc.contributor.authorLiu, Yen_US
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dc.contributor.authorPeacock, Men_US
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dc.contributor.authorVan Duijn, CMen_US
dc.contributor.authorWareham, NJen_US
dc.contributor.authorCupples, LAen_US
dc.contributor.authorEcons, MJen_US
dc.contributor.authorEvans, DMen_US
dc.contributor.authorHarris, TBen_US
dc.contributor.authorKung, AWCen_US
dc.contributor.authorPsaty, BMen_US
dc.contributor.authorReeve, Jen_US
dc.contributor.authorSpector, TDen_US
dc.contributor.authorStreeten, EAen_US
dc.contributor.authorZillikens, MCen_US
dc.contributor.authorThorsteinsdottir, Uen_US
dc.contributor.authorOhlsson, Cen_US
dc.contributor.authorKarasik, Den_US
dc.contributor.authorRichards, JBen_US
dc.contributor.authorBrown, MAen_US
dc.contributor.authorStefansson, Ken_US
dc.contributor.authorUitterlinden, AGen_US
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dc.date.accessioned2012-11-26T09:03:31Z-
dc.date.available2012-11-26T09:03:31Z-
dc.date.issued2012en_US
dc.identifier.citationNature Genetics, 2012, v. 44 n. 5, p. 491-501en_US
dc.identifier.issn1061-4036en_US
dc.identifier.urihttp://hdl.handle.net/10722/175990-
dc.description.abstractBone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10 -8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10 -4, Bonferroni corrected), of which six reached P < 5 × 10 -8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility. © 2012 Nature America, Inc. All rights reserved.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.comen_US
dc.relation.ispartofNature Geneticsen_US
dc.subject.meshBone Density - Geneticsen_US
dc.subject.meshComputational Biologyen_US
dc.subject.meshEuropean Continental Ancestry Groupen_US
dc.subject.meshExtracellular Matrix Proteins - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshFemur Neck - Physiopathologyen_US
dc.subject.meshFractures, Bone - Geneticsen_US
dc.subject.meshGene Expression Profilingen_US
dc.subject.meshGenetic Predisposition To Diseaseen_US
dc.subject.meshGenome-Wide Association Studyen_US
dc.subject.meshGenotypeen_US
dc.subject.meshGlycoproteins - Geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshIntercellular Signaling Peptides And Proteins - Geneticsen_US
dc.subject.meshLow Density Lipoprotein Receptor-Related Protein-5 - Geneticsen_US
dc.subject.meshLumbar Vertebrae - Physiopathologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMitochondrial Membrane Transport Proteins - Geneticsen_US
dc.subject.meshOsteoporosis - Geneticsen_US
dc.subject.meshPhosphoproteins - Geneticsen_US
dc.subject.meshPolymorphism, Single Nucleotide - Geneticsen_US
dc.subject.meshQuantitative Trait Locien_US
dc.subject.meshRisk Factorsen_US
dc.subject.meshSpectrin - Geneticsen_US
dc.titleGenome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fractureen_US
dc.typeArticleen_US
dc.identifier.emailSham, PC: pcsham@hku.hken_US
dc.identifier.authoritySham, PC=rp00459en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/ng.2249en_US
dc.identifier.pmid22504420-
dc.identifier.scopuseid_2-s2.0-84860331458en_US
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dc.identifier.volume44en_US
dc.identifier.issue5en_US
dc.identifier.spage491en_US
dc.identifier.epage501en_US
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dc.identifier.citeulike10572141-
dc.identifier.issnl1061-4036-

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