6533b833fe1ef96bd129b927
RESEARCH PRODUCT
Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
Henry VölzkeJonathan ReeveJonathan ReeveMaciej JaworskiOzren PolasekKristina ÅKessonMarcin KrukWilmar IglPeter P. PramstallerMatthew A. BrownRodney J. ScottUwe VölkerKarol EstradaMika KähönenHou-feng ZhengSu-mei XiaoFrances M K WilliamsScott WilsonScott WilsonScott WilsonHarri SievänenSteven BoonenDoug C. BauerDoug C. BauerIan R. ReidNicholas C. HarveyÖSten LjunggrenHarry CampbellFrederick C. W. WuGregory J. TranahGregory J. TranahDouglas P. KielAndrew A. HicksMelissa GarciaPriya SrikanthCaroline HaywardRosalie A. M. Dhonukshe-ruttenAnnie W.c. KungYongmei LiuLeo-pekka LyytikäinenCyrus CooperCyrus CooperStephen R PyeGeoffrey C. NicholsonElaine M. DennisonCarrie M. NielsonSteven R. CummingsSteven R. CummingsGraeme JonesYi-hsiang HsuGeorg HomuthAlireza MoayyeriFabiola Del Greco MNicole SoranzoFiona E. McguiganHenri WallaschofskiJohn AttiaAlexander TeumerMark McevoyTamara B. HarrisAlbert HofmanPak C. ShamMarkku AlenDirk VanderschuerenSuzanne J. BrownChristopher OldmeadowElizabeth G. HollidayGeorge DedoussisMaria Luisa BrandiAnke HannemannUlf GyllenstenRichard L. PrinceRichard L. PrinceYoon Shin ChoMarika LaaksonenJorma ViikariCarolina Medina-gomezJohanna JakobsdottirKay-tee KhawTim D. SpectorMin Jin GoStephen KaptogePaweł PłudowskiKristin SiggeirsdottirNathalie Van Der VeldeKarin M. A. SwartEugene V. MccloskeyEugene V. MccloskeySulin ChengRobin HaringAndré G. UitterlindenJosé L. HernándezSylvie GirouxEmma L. DuncanEmma L. DuncanTerho LehtimäkiJ. Brent RichardsJ. Brent RichardsPaul LeoJohn A. EismanAlbert V. SmithThor AspelundEric S. OrwollPaul LipsRobert LubenKate L. HollidayOlli T. RaitakariOlli T. RaitakariJong-young LeeDan MellströmEfi GrigoriouClaes OhlssonLaura MasiRoman S. LorencDavid KarasikYanhua ZhouNatasja M. Van SchoorRyan L. MinsterJohn D. WarkJoshua R. LewisJoshua R. LewisJoo-yeon HwangVilmundur GudnasonNicholas J. WarehamOlivia TrummerJoseph M. ZmudaLing OeiJesús González-macíasBarbara Obermayer-pietschRichard EastellTerence W O'neillÅSa JohanssonLisette C. P. G. M. De GrootRoseanne PeelMagnus KarlssonA.w. EnnemanJosé M. OlmosMatthias NauckKun ZhuKun ZhuChing-ti LiuFernando RivadeneiraJosé A. RianchoFrançois Rousseausubject
MaleOncologyHeelBone densityOsteoporosisGenome-wide association studyCohort StudiesFractures Bonequantitative ultrasoundBone DensityGenetics (clinical)riskUltrasonographyAged 80 and overGeneticsmedicine.diagnostic_testAssociation Studies Articlesphenotypesta3141General MedicineMiddle Aged3. Good healthmedicine.anatomical_structureosteoporosis diagnostic radiologic examination roentgen rays ultrasonography bone mineral density fractures calcaneus chromosomes genes genome heel longevity single nucleotide polymorphism sound genetics chromosome 7q31 genotype determination genome-wide association study attenuation osteoporotic fracture risk/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingFemalewomenAdultmusculoskeletal diseasesmedicine.medical_specialtyx-ray absorptiometrySingle-nucleotide polymorphismdensitometryBiologyPolymorphism Single NucleotidecalcaneusYoung AdultSDG 3 - Good Health and Well-beingInternal medicineGeneticsmedicineHumansGenetic Predisposition to DiseaseMolecular BiologyDual-energy X-ray absorptiometryVLAGAgedGlobal NutritionWereldvoedingta1184ta3121medicine.diseaseosteoporosisCalcaneusGenetic epidemiologyfractureOsteoporosismineral densityCalcaneusGenome-Wide Association Studydescription
Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-01-14 |