6533b857fe1ef96bd12b4e81
RESEARCH PRODUCT
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture
Barbara Obermayer-pietschNerea AlonsoSu-mei XiaoZoe H. DailianaDaniel I. ChasmanAndrew R. WoodGhi Su KimP. Eline SlagboomStephen KaptogeSjur ReppeL. B. HustedAndré G. UitterlindenJonathan ReeveEmma L. DuncanAnnie W.c. KungTomi PastinenPaul LeoGeorge DedoussisPaul LipsMatthias LorentzonDavid M. EvansLing OeiJohn A. EismanJohn A. EismanNelson Ls TangMarcin KrukHou-feng ZhengBrendan M. BuckleyKun ZhuSimona Mencej-bedračJames F. WilsonGeoffrey C. NicholsonSeung-hun LeeElaine M. DennisonCharles KooperbergMatthew A. BrownKarol EstradaAaron K. AragakiMartha C. Castaño-betancourtLaura MasiRyan L. MinsterGunnar SigurdssonJohn P. A. IoannidisJohn P. A. IoannidisGöran HallmansJ. Wouter JukemaTony KwanJohn P. KempRebecca D. JacksonAlireza MoayyeriJosé A. RianchoDominique J. VerlaanJoshua R. LewisJanez PrezeljClaus ChristiansenPaul M. RidkerElza KhusnutdinovaKhusainova RiRoman S. LorencDavid M. ReidYi-hsiang HsuClaes OhlssonChing-ti LiuKannabiran NandakumarNicholas J. WarehamLynda M. RoseAlbert V. SmithCarolina Medina-gomezEvangelia E. NtzaniCornelia M. Van DuijnKay-tee KhawGudmar ThorleifssonTamara B. HarrisP. C. LeungMillan S. PatelLaura M. Yerges-armstrongYanhua ZhouLynne J. HockingDan MellströmYongmei LiuFrances M K WilliamsAlan R. ShuldinerJanja MarcOmar M. E. AlbaghaTheodora KoromilaElizabeth A. StreetenFernando RivadeneiraBraxton D. MitchellKaren A. JamesonHrefna JohannsdottirL. Adrienne CupplesDouglas P. KielTim D. SpectorSulin ChengKristin SiggeirsdottirStuart H. RalstonRui Jian LiIan FordJ. Brent RichardsSerena ScollenScott WilsonScott WilsonGuo Shuai LiMika KähönenJean WooMunro PeacockMaría T. ZarrabeitiaSoumya RaychaudhuriSoumya RaychaudhuriHuibert A. P. PolsJohn A RobbinsMorten FrostMorten FrostWim Van HulAndrea Z. LacroixDavid KarasikNatasja M. Van SchoorYurii S. AulchenkoJorma ViikariBente L. LangdahlXavier NoguésMarika LaaksonenJung-min KohIan R. ReidDana WillnerStefan T PalssonOlle SvenssonRobert LubenMarkku AlenRichard L. PrinceDavid GoltzmanLizbeth HerreraThorvaldur IngvarssonOlli T. RaitakariOlli T. RaitakariSylvie GirouxKari StefanssonKari StefanssonPatrick DanoySusana BalcellsEugene V. MccloskeyPak C. ShamLiesbeth VandenputEvangelos EvangelouFrançois RousseauUnnur StyrkarsdottirJesús González-macíasAlbert HofmanGraeme R. ClarkM. Carola ZillikensSteven R. CummingsMagnus KarlssonPanagoula KolliaThor AspelundGraeme JonesWilliam D. LeslieBen A. OostraUnnur ThorsteinsdottirUnnur ThorsteinsdottirMaria Luisa BrandiStella TrompetMichael J. EconsOlivia TrummerUlrika Pettersson-kymmerJosé M. OlmosJane A. CauleyNatalia Garcia-giraltNajaf AminPhilip N. SambrookTerho LehtimäkiDaniel L. KollerDavid DugganJoyce B. J. Van MeursVille AaltoVille AaltoJoel ErikssonRoser UrreiztiVilmundur GudnasonKaare M. GautvikRichard EastellElin GrundbergElin GrundbergBruce M. PsatyCandace M. KammererJerome I. RotterÖSten LjunggrenMelissa Nolan GarciaCyrus CooperTuan V. NguyenTuan V. NguyenFrances A. Tylavskysubject
MaleBone densityOsteoporosisGenome-wide association studyMitochondrial Membrane Transport ProteinsBone densitometryFractures Bone0302 clinical medicineBone DensityRisk FactorsFemurGeneticsBone mineral0303 health scienceseducation.field_of_studyExtracellular Matrix ProteinsLumbar VertebraeFemur Neckta3141medicine.anatomical_structureLow Density Lipoprotein Receptor-Related Protein-5/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingIntercellular Signaling Peptides and ProteinsFemaleGensmusculoskeletal diseases/dk/atira/pure/subjectarea/asjc/1300/1311GenotypePopulationEuropean Continental Ancestry GroupQuantitative Trait Loci030209 endocrinology & metabolismVèrtebres lumbarsBiologyFèmurPolymorphism Single NucleotideArticleWhite People03 medical and health sciencesSDG 3 - Good Health and Well-beingDensitometria òssiaGeneticsmedicineHumansGenetic Predisposition to Diseaseeducation030304 developmental biologyFemoral neckGenetic associationGlycoproteinsGene Expression ProfilingComputational BiologySpectrinta3121medicine.diseasePhosphoproteinsGenesOsteoporosisMesenchymal stem cell differentiationHuman medicineFracturesGenome-Wide Association Studydescription
Bone 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-05-01 |