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. Olmos & 110 others L.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

Research output: Contribution to journalArticle

54 Citations (Scopus)

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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Calcaneus
Heel
Genome-Wide Association Study
Bone Density
Meta-Analysis
Genome
Computer Simulation
Osteoporosis
Single Nucleotide Polymorphism
X-Rays

Cite this

Moayyeri, A. ; Hsu, Y. ; Karasik, D. ; Estrada, K. ; Xiao, S. ; Nielson, C.M. ; Srikanth, P. ; Giroux, S.K. ; Wilson, Scott ; Zheng, H. ; Smith, A.V. ; Pye, S.R. ; Leo, P.J. ; Teumer, A. ; Hwang, J. ; Ohlsson, C. ; Mcguigan, F.E.A. ; Minster, R.L. ; Hayward, C. ; Olmos, J.M. ; Lyytikäinen, L.P. ; Lewis, Joshua ; Swart, K.M.A. ; Masi, L. ; Oldmeadow, C.J. ; Holliday, E.G. ; Cheng, S. ; Van Schoor, N.M. ; Harvey, N.C.W. ; Kruk, M. ; Del Greco, F.M. ; Igl, W. ; Trummer, O. ; Grigoriou, E. ; Luben, R.N. ; Liu, C. ; Zhou, Y. ; Oei, L.D.W. ; Medina-Gõmez, C. ; Zmuda, J.M. ; Tranah, G.J. ; Brown, S.J. ; Williams, F.M.K. ; Soranzo, N. ; Jakobsdottir, J. ; Siggeirsdóttir, K. ; Holliday, K.L. ; Hannemann, A. ; Go, M. ; Garcia, M.E. ; Polašek, O. ; Laaksonen, M.M.L. ; Zhu, Kun ; Enneman, A.W. ; Mcevoy, M.A. ; Pee, R. ; Sham, P. ; Jaworski, M. ; Johansson, A.M. ; Hicks, A.A. ; Płudowski, P. ; Scott, R.J. ; Dhonukshe-Rutten, R.A.M. ; Van Der Velde, N.V. ; Kaöhönen, M. ; Viikari, J.S.A. ; Sievaönen, H. ; Raitakari, O.T. ; González-Macías, J.J. ; Hernández, J.L.Z. ; Mellström, D.D. ; Ljunggren, O. ; Cho, Y. ; Völker, U.U. ; Nauck, M.A. ; Homuth, G. ; Völzke, H. ; Haring, R. ; Brown, M.A. ; Mccloskey, E.V. ; Nicholson, G.C. ; Eastell, R. ; Eisman, J.A. ; Jones, G. ; Reid, I.R. ; Dennison, E.M. ; Wark, J.D. ; Boonen, S. ; Vanderschueren, D.M.O.I. ; Wu, F.C.W. ; Aspelund, T. ; Richards, J.B. ; Bauer, D.C. ; Hofman, A. ; Khaw, K.T.T. ; Dedoussis, G.V.Z. ; Obermayer-Pietsch, B.M. ; Gyllensten, U.B. ; Pramstaller, P.P. ; Lorenc, R.S. ; Cooper, C.C. ; Kung, A. ; Lips, P.T.A.M. ; Alén, M.J. ; Attia, J.R. ; Brandi, M.L. ; De Groot, L.C.P.G.M. ; Lehtimäki, T.J. ; Riancho, J.A. ; Campbell, H.S. ; Liu, Y. ; Harris, T.B. ; Åkesson, K. ; Karlsson, M.K. ; Jong-Lee, Y. ; Wallaschofski, H. ; Duncan, E.L. ; O'Neill, T.W. ; Gudnason, V.G. ; Spector, T.D. ; Rousseau, F.L. ; Orwoll, E.S. ; Cummings, S.R. ; Wareham, N.J. ; Rivadeneira, F.F. ; Uitterlinden, A.G. ; Prince, Richard ; Kiel, D.P. ; Reeve, J. ; Kaptoge, S.K. / Genetic determinants of heel bone properties: Genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium. In: Human Molecular Genetics. 2014 ; Vol. 23, No. 11. pp. 3054-3068.
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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",
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Moayyeri, A, Hsu, Y, Karasik, D, Estrada, K, Xiao, S, Nielson, CM, Srikanth, P, Giroux, SK, Wilson, S, Zheng, H, Smith, AV, Pye, SR, Leo, PJ, Teumer, A, Hwang, J, Ohlsson, C, Mcguigan, FEA, Minster, RL, Hayward, C, Olmos, JM, Lyytikäinen, LP, Lewis, J, Swart, KMA, Masi, L, Oldmeadow, CJ, Holliday, EG, Cheng, S, Van Schoor, NM, Harvey, NCW, Kruk, M, Del Greco, FM, Igl, W, Trummer, O, Grigoriou, E, Luben, RN, Liu, C, Zhou, Y, Oei, LDW, Medina-Gõmez, C, Zmuda, JM, Tranah, GJ, Brown, SJ, Williams, FMK, Soranzo, N, Jakobsdottir, J, Siggeirsdóttir, K, Holliday, KL, Hannemann, A, Go, M, Garcia, ME, Polašek, O, Laaksonen, MML, Zhu, K, Enneman, AW, Mcevoy, MA, Pee, R, Sham, P, Jaworski, M, Johansson, AM, Hicks, AA, Płudowski, P, Scott, RJ, Dhonukshe-Rutten, RAM, Van Der Velde, NV, Kaöhönen, M, Viikari, JSA, Sievaönen, H, Raitakari, OT, González-Macías, JJ, Hernández, JLZ, Mellström, DD, Ljunggren, O, Cho, Y, Völker, UU, Nauck, MA, Homuth, G, Völzke, H, Haring, R, Brown, MA, Mccloskey, EV, Nicholson, GC, Eastell, R, Eisman, JA, Jones, G, Reid, IR, Dennison, EM, Wark, JD, Boonen, S, Vanderschueren, DMOI, Wu, FCW, Aspelund, T, Richards, JB, Bauer, DC, Hofman, A, Khaw, KTT, Dedoussis, GVZ, Obermayer-Pietsch, BM, Gyllensten, UB, Pramstaller, PP, Lorenc, RS, Cooper, CC, Kung, A, Lips, PTAM, Alén, MJ, Attia, JR, Brandi, ML, De Groot, LCPGM, Lehtimäki, TJ, Riancho, JA, Campbell, HS, Liu, Y, Harris, TB, Åkesson, K, Karlsson, MK, Jong-Lee, Y, Wallaschofski, H, Duncan, EL, O'Neill, TW, Gudnason, VG, Spector, TD, Rousseau, FL, Orwoll, ES, Cummings, SR, Wareham, NJ, Rivadeneira, FF, Uitterlinden, AG, Prince, R, Kiel, DP, Reeve, J & Kaptoge, SK 2014, 'Genetic determinants of heel bone properties: Genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium' Human Molecular Genetics, vol. 23, no. 11, pp. 3054-3068. https://doi.org/10.1093/hmg/ddt675

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

In: Human Molecular Genetics, Vol. 23, No. 11, 2014, p. 3054-3068.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic determinants of heel bone properties: Genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

AU - Moayyeri, A.

AU - Hsu, Y.

AU - Karasik, D.

AU - Estrada, K.

AU - Xiao, S.

AU - Nielson, C.M.

AU - Srikanth, P.

AU - Giroux, S.K.

AU - Wilson, Scott

AU - Zheng, H.

AU - Smith, A.V.

AU - Pye, S.R.

AU - Leo, P.J.

AU - Teumer, A.

AU - Hwang, J.

AU - Ohlsson, C.

AU - Mcguigan, F.E.A.

AU - Minster, R.L.

AU - Hayward, C.

AU - Olmos, J.M.

AU - Lyytikäinen, L.P.

AU - Lewis, Joshua

AU - Swart, K.M.A.

AU - Masi, L.

AU - Oldmeadow, C.J.

AU - Holliday, E.G.

AU - Cheng, S.

AU - Van Schoor, N.M.

AU - Harvey, N.C.W.

AU - Kruk, M.

AU - Del Greco, F.M.

AU - Igl, W.

AU - Trummer, O.

AU - Grigoriou, E.

AU - Luben, R.N.

AU - Liu, C.

AU - Zhou, Y.

AU - Oei, L.D.W.

AU - Medina-Gõmez, C.

AU - Zmuda, J.M.

AU - Tranah, G.J.

AU - Brown, S.J.

AU - Williams, F.M.K.

AU - Soranzo, N.

AU - Jakobsdottir, J.

AU - Siggeirsdóttir, K.

AU - Holliday, K.L.

AU - Hannemann, A.

AU - Go, M.

AU - Garcia, M.E.

AU - Polašek, O.

AU - Laaksonen, M.M.L.

AU - Zhu, Kun

AU - Enneman, A.W.

AU - Mcevoy, M.A.

AU - Pee, R.

AU - Sham, P.

AU - Jaworski, M.

AU - Johansson, A.M.

AU - Hicks, A.A.

AU - Płudowski, P.

AU - Scott, R.J.

AU - Dhonukshe-Rutten, R.A.M.

AU - Van Der Velde, N.V.

AU - Kaöhönen, M.

AU - Viikari, J.S.A.

AU - Sievaönen, H.

AU - Raitakari, O.T.

AU - González-Macías, J.J.

AU - Hernández, J.L.Z.

AU - Mellström, D.D.

AU - Ljunggren, O.

AU - Cho, Y.

AU - Völker, U.U.

AU - Nauck, M.A.

AU - Homuth, G.

AU - Völzke, H.

AU - Haring, R.

AU - Brown, M.A.

AU - Mccloskey, E.V.

AU - Nicholson, G.C.

AU - Eastell, R.

AU - Eisman, J.A.

AU - Jones, G.

AU - Reid, I.R.

AU - Dennison, E.M.

AU - Wark, J.D.

AU - Boonen, S.

AU - Vanderschueren, D.M.O.I.

AU - Wu, F.C.W.

AU - Aspelund, T.

AU - Richards, J.B.

AU - Bauer, D.C.

AU - Hofman, A.

AU - Khaw, K.T.T.

AU - Dedoussis, G.V.Z.

AU - Obermayer-Pietsch, B.M.

AU - Gyllensten, U.B.

AU - Pramstaller, P.P.

AU - Lorenc, R.S.

AU - Cooper, C.C.

AU - Kung, A.

AU - Lips, P.T.A.M.

AU - Alén, M.J.

AU - Attia, J.R.

AU - Brandi, M.L.

AU - De Groot, L.C.P.G.M.

AU - Lehtimäki, T.J.

AU - Riancho, J.A.

AU - Campbell, H.S.

AU - Liu, Y.

AU - Harris, T.B.

AU - Åkesson, K.

AU - Karlsson, M.K.

AU - Jong-Lee, Y.

AU - Wallaschofski, H.

AU - Duncan, E.L.

AU - O'Neill, T.W.

AU - Gudnason, V.G.

AU - Spector, T.D.

AU - Rousseau, F.L.

AU - Orwoll, E.S.

AU - Cummings, S.R.

AU - Wareham, N.J.

AU - Rivadeneira, F.F.

AU - Uitterlinden, A.G.

AU - Prince, Richard

AU - Kiel, D.P.

AU - Reeve, J.

AU - Kaptoge, S.K.

PY - 2014

Y1 - 2014

N2 - 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

AB - 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

U2 - 10.1093/hmg/ddt675

DO - 10.1093/hmg/ddt675

M3 - Article

VL - 23

SP - 3054

EP - 3068

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 11

ER -