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

A. Moayyeri; Y.H. Hsu; D. Karasik; K. Estrada; S.M. Xiao; C. Nielson; P. Srikanth; S. Giroux; S.G. Wilson; H.F. Zheng; A.V. Smith; S.R. Pye; P.J. Leo; A. Teumer; J.Y. Hwang; C. Ohlsson; F. McGuigan; R.L. Minster; C. Hayward; J.M. Olmos; L.P. Lyytikainen; J.R. Lewis; K.M.A. Swart; L. Masi; C. Oldmeadow; E.G. Holliday; S.L. Cheng; N.M. van Schoor; N.C. Harvey; M. Kruk; M. Fabiola Del Greco; W. Igl; O. Trummer; E. Grigoriou; R. Luben; C.T. Liu; Y.H. Zhou; L. Oei; C. Medina-Gomez; J. Zmuda; G. Tranah; S.J. Brown; F.M. Williams; N. Soranzo; J. Jakobsdottir; K. Siggeirsdottir; K.L. Holliday; A. Hannemann; M.J. Go; M. Garcia; O. Polasek; M. Laaksonen; K. Zhu; A.W. Enneman; M. McEvoy; R. Peel; P.C. Sham; M. Jaworski; A. Johansson; A.A. Hicks; P. Pludowski; R. Scott; R.A.M. Dhonukshe-Rutten; N. van der Velde; M. Kahonen; J.S. Viikari; H. Sievanen; O.T. Raitakari; J. Gonzalez-Macias; J.L. Hernandez; D. Mellstroom; O. Ljunggren; Y.S. Cho; U. Volker; M. Nauck; G. Homuth; H. Volzke; R. Haring; M. A. Brown; E. McCloskey; G.C. Nicholson; R. Eastell; J.A. Eisman; G. Jones; I.R. Reid; E.M. Dennison; J. Wark; S. Boonen; D. Vanderschueren; F.C.W. Wu; T. Aspelund; J.B. Richards; D. Bauer; A. Hofman; K.T. Khaw; G. Dedoussis; B. Obermayer-Pietsch; U. Gyllensten; P.P. Pramstaller; R.S. Lorenc; C. Cooper; A.W.C. Kung; P.T.A.M. Lips; J. Reeve; S.K. Kaptoge; Leo-Pekka Lyytikäinen; Fabiola del Greco M; Mika Kähönen; Harri Sievänen; Dan Mellström; Uwe Völker; Henry Völzke; Markku Alen; John Attia; Maria Luisa Brandi; Lisette C. P. G. M. de Groot; Terho Lehtimäki; José A. Riancho; Harry Campbell; Yongmei Liu; Tamara B. Harris; Kristina Akesson; Magnus Karlsson; Jong-Young Lee; Henri Wallaschofski; Emma L. Duncan; Terence W. O'Neill; Vilmundur Gudnason; Timothy D. Spector; François Rousseau; Eric Orwoll; Steven R. Cummings; Nick J. Wareham; Fernando Rivadeneira; Andre G. Uitterlinden; Richard L. Prince; Douglas P. Kiel

doi: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

A. Moayyeri, Y.H. Hsu, D. Karasik, K. Estrada, S.M. Xiao, C. Nielson, P. Srikanth, S. Giroux, S.G. Wilson, H.F. Zheng, A.V. Smith, S.R. Pye, P.J. Leo, A. Teumer, J.Y. Hwang, C. Ohlsson, F. McGuigan, R.L. Minster, C. Hayward, J.M. OlmosL.P. Lyytikainen, J.R. Lewis, K.M.A. Swart, L. Masi, C. Oldmeadow, E.G. Holliday, S.L. Cheng, N.M. van Schoor, N.C. Harvey, M. Kruk, M. Fabiola Del Greco, W. Igl, O. Trummer, E. Grigoriou, R. Luben, C.T. Liu, Y.H. Zhou, L. Oei, C. Medina-Gomez, J. Zmuda, G. Tranah, S.J. Brown, F.M. Williams, N. Soranzo, J. Jakobsdottir, K. Siggeirsdottir, K.L. Holliday, A. Hannemann, M.J. Go, M. Garcia, O. Polasek, M. Laaksonen, K. Zhu, A.W. Enneman, M. McEvoy, R. Peel, P.C. Sham, M. Jaworski, A. Johansson, A.A. Hicks, P. Pludowski, R. Scott, R.A.M. Dhonukshe-Rutten, N. van der Velde, M. Kahonen, J.S. Viikari, H. Sievanen, O.T. Raitakari, J. Gonzalez-Macias, J.L. Hernandez, D. Mellstroom, O. Ljunggren, Y.S. Cho, U. Volker, M. Nauck, G. Homuth, H. Volzke, R. Haring, M. A. Brown, E. McCloskey, G.C. Nicholson, R. Eastell, J.A. Eisman, G. Jones, I.R. Reid, E.M. Dennison, J. Wark, S. Boonen, D. Vanderschueren, F.C.W. Wu, T. Aspelund, J.B. Richards, D. Bauer, A. Hofman, K.T. Khaw, G. Dedoussis, B. Obermayer-Pietsch, U. Gyllensten, P.P. Pramstaller, R.S. Lorenc, C. Cooper, A.W.C. Kung, P.T.A.M. Lips, J. Reeve, S.K. Kaptoge, Leo-Pekka Lyytikäinen, Fabiola del Greco M, Mika Kähönen, Harri Sievänen, Dan Mellström, Uwe Völker, Henry Völzke, Markku Alen, John Attia, Maria Luisa Brandi, Lisette C. P. G. M. de Groot, Terho Lehtimäki, José A. Riancho, Harry Campbell, Yongmei Liu, Tamara B. Harris, Kristina Akesson, Magnus Karlsson, Jong-Young Lee, Henri Wallaschofski, Emma L. Duncan, Terence W. O'Neill, Vilmundur Gudnason, Timothy D. Spector, François Rousseau, Eric Orwoll, Steven R. Cummings, Nick J. Wareham, Fernando Rivadeneira, Andre G. Uitterlinden, Richard L. Prince, Douglas P. Kiel

Research output: Contribution to journal › Article › Academic › peer-review

78 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 = 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 × 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 × 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 × 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

Original language	English
Pages (from-to)	3054-3068
Journal	Human Molecular Genetics
Volume	23
Issue number	11
DOIs	https://doi.org/10.1093/hmg/ddt675
Publication status	Published - 2014

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Cite this

Moayyeri, A., Hsu, Y. H., Karasik, D., Estrada, K., Xiao, S. M., Nielson, C., Srikanth, P., Giroux, S., Wilson, S. G., Zheng, H. F., Smith, A. V., Pye, S. R., Leo, P. J., Teumer, A., Hwang, J. Y., Ohlsson, C., McGuigan, F., Minster, R. L., Hayward, C., ... Kiel, D. P. (2014). Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium. Human Molecular Genetics, 23(11), 3054-3068. https://doi.org/10.1093/hmg/ddt675

@article{c56328bdc83e4efea74216a6dc1210d4,

title = "Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium",

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 = 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 × 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 × 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 × 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",

author = "A. Moayyeri and Y.H. Hsu and D. Karasik and K. Estrada and S.M. Xiao and C. Nielson and P. Srikanth and S. Giroux and S.G. Wilson and H.F. Zheng and A.V. Smith and S.R. Pye and P.J. Leo and A. Teumer and J.Y. Hwang and C. Ohlsson and F. McGuigan and R.L. Minster and C. Hayward and J.M. Olmos and L.P. Lyytikainen and J.R. Lewis and K.M.A. Swart and L. Masi and C. Oldmeadow and E.G. Holliday and S.L. Cheng and {van Schoor}, N.M. and N.C. Harvey and M. Kruk and {Fabiola Del Greco}, M. and W. Igl and O. Trummer and E. Grigoriou and R. Luben and C.T. Liu and Y.H. Zhou and L. Oei and C. Medina-Gomez and J. Zmuda and G. Tranah and S.J. Brown and F.M. Williams and N. Soranzo and J. Jakobsdottir and K. Siggeirsdottir and K.L. Holliday and A. Hannemann and M.J. Go and M. Garcia and O. Polasek and M. Laaksonen and K. Zhu and A.W. Enneman and M. McEvoy and R. Peel and P.C. Sham and M. Jaworski and A. Johansson and A.A. Hicks and P. Pludowski and R. Scott and R.A.M. Dhonukshe-Rutten and {van der Velde}, N. and M. Kahonen and J.S. Viikari and H. Sievanen and O.T. Raitakari and J. Gonzalez-Macias and J.L. Hernandez and D. Mellstroom and O. Ljunggren and Y.S. Cho and U. Volker and M. Nauck and G. Homuth and H. Volzke and R. Haring and Brown, {M. A.} and E. McCloskey and G.C. Nicholson and R. Eastell and J.A. Eisman and G. Jones and I.R. Reid and E.M. Dennison and J. Wark and S. Boonen and D. Vanderschueren and F.C.W. Wu and T. Aspelund and J.B. Richards and D. Bauer and A. Hofman and K.T. Khaw and G. Dedoussis and B. Obermayer-Pietsch and U. Gyllensten and P.P. Pramstaller and R.S. Lorenc and C. Cooper and A.W.C. Kung and P.T.A.M. Lips and J. Reeve and S.K. Kaptoge and Leo-Pekka Lyytik{\"a}inen and {del Greco M}, Fabiola and Mika K{\"a}h{\"o}nen and Harri Siev{\"a}nen and Dan Mellstr{\"o}m and Uwe V{\"o}lker and Henry V{\"o}lzke and Markku Alen and John Attia and Brandi, {Maria Luisa} and {de Groot}, {Lisette C. P. G. M.} and Terho Lehtim{\"a}ki and Riancho, {Jos{\'e} A.} and Harry Campbell and Yongmei Liu and Harris, {Tamara B.} and Kristina Akesson and Magnus Karlsson and Jong-Young Lee and Henri Wallaschofski and Duncan, {Emma L.} and O'Neill, {Terence W.} and Vilmundur Gudnason and Spector, {Timothy D.} and Fran{\c c}ois Rousseau and Eric Orwoll and Cummings, {Steven R.} and Wareham, {Nick J.} and Fernando Rivadeneira and Uitterlinden, {Andre G.} and Prince, {Richard L.} and Kiel, {Douglas P.}",

year = "2014",

doi = "https://doi.org/10.1093/hmg/ddt675",

language = "English",

volume = "23",

pages = "3054--3068",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "11",

}

Moayyeri, A, Hsu, YH, Karasik, D, Estrada, K, Xiao, SM, Nielson, C, Srikanth, P, Giroux, S, Wilson, SG, Zheng, HF, Smith, AV, Pye, SR, Leo, PJ, Teumer, A, Hwang, JY, Ohlsson, C, McGuigan, F, Minster, RL, Hayward, C, Olmos, JM, Lyytikainen, LP, Lewis, JR, Swart, KMA, Masi, L, Oldmeadow, C, Holliday, EG, Cheng, SL, van Schoor, NM, Harvey, NC, Kruk, M, Fabiola Del Greco, M, Igl, W, Trummer, O, Grigoriou, E, Luben, R, Liu, CT, Zhou, YH, Oei, L, Medina-Gomez, C, Zmuda, J, Tranah, G, Brown, SJ, Williams, FM, Soranzo, N, Jakobsdottir, J, Siggeirsdottir, K, Holliday, KL, Hannemann, A, Go, MJ, Garcia, M, Polasek, O, Laaksonen, M, Zhu, K, Enneman, AW, McEvoy, M, Peel, R, Sham, PC, Jaworski, M, Johansson, A, Hicks, AA, Pludowski, P, Scott, R, Dhonukshe-Rutten, RAM, van der Velde, N, Kahonen, M, Viikari, JS, Sievanen, H, Raitakari, OT, Gonzalez-Macias, J, Hernandez, JL, Mellstroom, D, Ljunggren, O, Cho, YS, Volker, U, Nauck, M, Homuth, G, Volzke, H, Haring, R, Brown, MA, McCloskey, E, Nicholson, GC, Eastell, R, Eisman, JA, Jones, G, Reid, IR, Dennison, EM, Wark, J, Boonen, S, Vanderschueren, D, Wu, FCW, Aspelund, T, Richards, JB, Bauer, D, Hofman, A, Khaw, KT, Dedoussis, G, Obermayer-Pietsch, B, Gyllensten, U, Pramstaller, PP, Lorenc, RS, Cooper, C, Kung, AWC, Lips, PTAM, Reeve, J, Kaptoge, SK, Lyytikäinen, L-P, del Greco M, F, Kähönen, M, Sievänen, H, Mellström, D, Völker, U, Völzke, H, Alen, M, Attia, J, Brandi, ML, de Groot, LCPGM, Lehtimäki, T, Riancho, JA, Campbell, H, Liu, Y, Harris, TB, Akesson, K, Karlsson, M, Lee, J-Y, Wallaschofski, H, Duncan, EL, O'Neill, TW, Gudnason, V, Spector, TD, Rousseau, F, Orwoll, E, Cummings, SR, Wareham, NJ, Rivadeneira, F, Uitterlinden, AG, Prince, RL & Kiel, DP 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

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.H.

AU - Karasik, D.

AU - Estrada, K.

AU - Xiao, S.M.

AU - Nielson, C.

AU - Srikanth, P.

AU - Giroux, S.

AU - Wilson, S.G.

AU - Zheng, H.F.

AU - Smith, A.V.

AU - Pye, S.R.

AU - Leo, P.J.

AU - Teumer, A.

AU - Hwang, J.Y.

AU - Ohlsson, C.

AU - McGuigan, F.

AU - Minster, R.L.

AU - Hayward, C.

AU - Olmos, J.M.

AU - Lyytikainen, L.P.

AU - Lewis, J.R.

AU - Swart, K.M.A.

AU - Masi, L.

AU - Oldmeadow, C.

AU - Holliday, E.G.

AU - Cheng, S.L.

AU - van Schoor, N.M.

AU - Harvey, N.C.

AU - Kruk, M.

AU - Fabiola Del Greco, M.

AU - Igl, W.

AU - Trummer, O.

AU - Grigoriou, E.

AU - Luben, R.

AU - Liu, C.T.

AU - Zhou, Y.H.

AU - Oei, L.

AU - Medina-Gomez, C.

AU - Zmuda, J.

AU - Tranah, G.

AU - Brown, S.J.

AU - Williams, F.M.

AU - Soranzo, N.

AU - Jakobsdottir, J.

AU - Siggeirsdottir, K.

AU - Holliday, K.L.

AU - Hannemann, A.

AU - Go, M.J.

AU - Garcia, M.

AU - Polasek, O.

AU - Laaksonen, M.

AU - Zhu, K.

AU - Enneman, A.W.

AU - McEvoy, M.

AU - Peel, R.

AU - Sham, P.C.

AU - Jaworski, M.

AU - Johansson, A.

AU - Hicks, A.A.

AU - Pludowski, P.

AU - Scott, R.

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

AU - van der Velde, N.

AU - Kahonen, M.

AU - Viikari, J.S.

AU - Sievanen, H.

AU - Raitakari, O.T.

AU - Gonzalez-Macias, J.

AU - Hernandez, J.L.

AU - Mellstroom, D.

AU - Ljunggren, O.

AU - Cho, Y.S.

AU - Volker, U.

AU - Nauck, M.

AU - Homuth, G.

AU - Volzke, H.

AU - Haring, R.

AU - Brown, M. A.

AU - McCloskey, E.

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.

AU - Boonen, S.

AU - Vanderschueren, D.

AU - Wu, F.C.W.

AU - Aspelund, T.

AU - Richards, J.B.

AU - Bauer, D.

AU - Hofman, A.

AU - Khaw, K.T.

AU - Dedoussis, G.

AU - Obermayer-Pietsch, B.

AU - Gyllensten, U.

AU - Pramstaller, P.P.

AU - Lorenc, R.S.

AU - Cooper, C.

AU - Kung, A.W.C.

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

AU - Reeve, J.

AU - Kaptoge, S.K.

AU - Lyytikäinen, Leo-Pekka

AU - del Greco M, Fabiola

AU - Kähönen, Mika

AU - Sievänen, Harri

AU - Mellström, Dan

AU - Völker, Uwe

AU - Völzke, Henry

AU - Alen, Markku

AU - Attia, John

AU - Brandi, Maria Luisa

AU - de Groot, Lisette C. P. G. M.

AU - Lehtimäki, Terho

AU - Riancho, José A.

AU - Campbell, Harry

AU - Liu, Yongmei

AU - Harris, Tamara B.

AU - Akesson, Kristina

AU - Karlsson, Magnus

AU - Lee, Jong-Young

AU - Wallaschofski, Henri

AU - Duncan, Emma L.

AU - O'Neill, Terence W.

AU - Gudnason, Vilmundur

AU - Spector, Timothy D.

AU - Rousseau, François

AU - Orwoll, Eric

AU - Cummings, Steven R.

AU - Wareham, Nick J.

AU - Rivadeneira, Fernando

AU - Uitterlinden, Andre G.

AU - Prince, Richard L.

AU - Kiel, Douglas P.

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 = 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 × 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 × 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 × 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

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 = 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 × 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 × 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 × 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

U2 - https://doi.org/10.1093/hmg/ddt675

DO - https://doi.org/10.1093/hmg/ddt675

M3 - Article

C2 - 24430505

SN - 0964-6906

VL - 23

SP - 3054

EP - 3068

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 11

ER -