Genetic determinants of heel bone properties: Genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

A. Moayyeri, Y. Hsu, D. Karasik, K. Estrada, S. Xiao, C.M. Nielson, P. Srikanth, S.K. Giroux, Scott Wilson, H. Zheng, A.V. Smith, S.R. Pye, P.J. Leo, A. Teumer, J. Hwang, C. Ohlsson, F.E.A. Mcguigan, R.L. Minster, C. Hayward, J.M. OlmosL.P. Lyytikäinen, Joshua Lewis, K.M.A. Swart, L. Masi, C.J. Oldmeadow, E.G. Holliday, S. Cheng, N.M. Van Schoor, N.C.W. Harvey, M. Kruk, F.M. Del Greco, W. Igl, O. Trummer, E. Grigoriou, R.N. Luben, C. Liu, Y. Zhou, L.D.W. Oei, C. Medina-Gõmez, J.M. Zmuda, G.J. Tranah, S.J. Brown, F.M.K. Williams, N. Soranzo, J. Jakobsdottir, K. Siggeirsdóttir, K.L. Holliday, A. Hannemann, M. Go, M.E. Garcia, O. Polašek, M.M.L. Laaksonen, Kun Zhu, A.W. Enneman, M.A. Mcevoy, R. Pee, P. Sham, M. Jaworski, A.M. Johansson, A.A. Hicks, P. Płudowski, R.J. Scott, R.A.M. Dhonukshe-Rutten, N.V. Van Der Velde, M. Kaöhönen, J.S.A. Viikari, H. Sievaönen, O.T. Raitakari, J.J. González-Macías, J.L.Z. Hernández, D.D. Mellström, O. Ljunggren, Y. Cho, U.U. Völker, M.A. Nauck, G. Homuth, H. Völzke, R. Haring, M.A. Brown, E.V. Mccloskey, G.C. Nicholson, R. Eastell, J.A. Eisman, G. Jones, I.R. Reid, E.M. Dennison, J.D. Wark, S. Boonen, D.M.O.I. Vanderschueren, F.C.W. Wu, T. Aspelund, J.B. Richards, D.C. Bauer, A. Hofman, K.T.T. Khaw, G.V.Z. Dedoussis, B.M. Obermayer-Pietsch, U.B. Gyllensten, P.P. Pramstaller, R.S. Lorenc, C.C. Cooper, A. Kung, P.T.A.M. Lips, M.J. Alén, J.R. Attia, M.L. Brandi, L.C.P.G.M. De Groot, T.J. Lehtimäki, J.A. Riancho, H.S. Campbell, Y. Liu, T.B. Harris, K. Åkesson, M.K. Karlsson, Y. Jong-Lee, H. Wallaschofski, E.L. Duncan, T.W. O'Neill, V.G. Gudnason, T.D. Spector, F.L. Rousseau, E.S. Orwoll, S.R. Cummings, N.J. Wareham, F.F. Rivadeneira, A.G. Uitterlinden, Richard Prince, D.P. Kiel, J. Reeve, S.K. Kaptoge

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Abstract

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 5 14 260), velocity of sound (VOS; n 5 15 514) and BMD (n 5 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n 5 11 452) and new genotyping in 15 cohorts (de novo n 5 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P
Original languageEnglish
Pages (from-to)3054-3068
JournalHuman Molecular Genetics
Volume23
Issue number11
DOIs
Publication statusPublished - 2014

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