The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men

Kate L. Holliday; Stephen R. Pye; Wendy Thomson; Steven Boonen; Herman Borghs; Dirk Vanderschueren; Evelien Gielen; Ilpo T. Huhtaniemi; Judith E. Adams; Kate A. Ward; Gyorgy Bartfai; Felipe Casanueva; Joseph D. Finn; Gianni Forti; Aleksander Giwercman; Thang S. Han; Krzysztof Kula; Fernand Labrie; Michael E J Lean; Neil Pendleton; Margus Punab; Frederick C W Wu; Terence W. O'Neill; EMAS Study Group

doi:10.1371/journal.pone.0022037

The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men

Kate L. Holliday, Stephen R. Pye, Wendy Thomson, Steven Boonen, Herman Borghs, Dirk Vanderschueren, Evelien Gielen, Ilpo T. Huhtaniemi, Judith E. Adams, Kate A. Ward, Gyorgy Bartfai, Felipe Casanueva, Joseph D. Finn, Gianni Forti, Aleksander Giwercman, Thang S. Han, Krzysztof Kula, Fernand Labrie, Michael E J Lean, Neil PendletonMargus Punab, Frederick C W Wu, Terence W. O'Neill, EMAS Study Group

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

Abstract

Purpose: Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor α gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMDa) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men. Methods: Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression. Results: 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMDa, a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMDa and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness. Conclusions: Our data replicate previous associations found between SNPs in the 6q25 locus and BMDa at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD. © 2011 Holliday et al.

Original language	English
Article number	e22037
Journal	PLoS ONE
Volume	6
Issue number	7
DOIs	https://doi.org/10.1371/journal.pone.0022037
Publication status	Published - 2011

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Holliday, K. L., Pye, S. R., Thomson, W., Boonen, S., Borghs, H., Vanderschueren, D., Gielen, E., Huhtaniemi, I. T., Adams, J. E., Ward, K. A., Bartfai, G., Casanueva, F., Finn, J. D., Forti, G., Giwercman, A., Han, T. S., Kula, K., Labrie, F., Lean, M. E. J., ... EMAS Study Group (2011). The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men. PLoS ONE, 6(7), Article e22037. https://doi.org/10.1371/journal.pone.0022037

@article{44e5b4d48cd44fc581bcf7ee939ad3f1,

title = "The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men",

abstract = "Purpose: Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor α gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMDa) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men. Methods: Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression. Results: 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMDa, a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMDa and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness. Conclusions: Our data replicate previous associations found between SNPs in the 6q25 locus and BMDa at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD. {\textcopyright} 2011 Holliday et al.",

author = "Holliday, {Kate L.} and Pye, {Stephen R.} and Wendy Thomson and Steven Boonen and Herman Borghs and Dirk Vanderschueren and Evelien Gielen and Huhtaniemi, {Ilpo T.} and Adams, {Judith E.} and Ward, {Kate A.} and Gyorgy Bartfai and Felipe Casanueva and Finn, {Joseph D.} and Gianni Forti and Aleksander Giwercman and Han, {Thang S.} and Krzysztof Kula and Fernand Labrie and Lean, {Michael E J} and Neil Pendleton and Margus Punab and Wu, {Frederick C W} and O'Neill, {Terence W.} and {EMAS Study Group}",

year = "2011",

doi = "10.1371/journal.pone.0022037",

language = "English",

volume = "6",

journal = "PLoS ONE",

publisher = "Public Library of Science",

number = "7",

}

Holliday, KL, Pye, SR, Thomson, W, Boonen, S, Borghs, H, Vanderschueren, D, Gielen, E, Huhtaniemi, IT, Adams, JE, Ward, KA, Bartfai, G, Casanueva, F, Finn, JD, Forti, G, Giwercman, A, Han, TS, Kula, K, Labrie, F, Lean, MEJ, Pendleton, N, Punab, M, Wu, FCW , O'Neill, TW & EMAS Study Group 2011, 'The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men', PLoS ONE, vol. 6, no. 7, e22037. https://doi.org/10.1371/journal.pone.0022037

TY - JOUR

T1 - The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men

AU - Holliday, Kate L.

AU - Pye, Stephen R.

AU - Thomson, Wendy

AU - Boonen, Steven

AU - Borghs, Herman

AU - Vanderschueren, Dirk

AU - Gielen, Evelien

AU - Huhtaniemi, Ilpo T.

AU - Adams, Judith E.

AU - Ward, Kate A.

AU - Bartfai, Gyorgy

AU - Casanueva, Felipe

AU - Finn, Joseph D.

AU - Forti, Gianni

AU - Giwercman, Aleksander

AU - Han, Thang S.

AU - Kula, Krzysztof

AU - Labrie, Fernand

AU - Lean, Michael E J

AU - Pendleton, Neil

AU - Punab, Margus

AU - Wu, Frederick C W

AU - O'Neill, Terence W.

AU - EMAS Study Group

PY - 2011

Y1 - 2011

N2 - Purpose: Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor α gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMDa) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men. Methods: Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression. Results: 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMDa, a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMDa and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness. Conclusions: Our data replicate previous associations found between SNPs in the 6q25 locus and BMDa at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD. © 2011 Holliday et al.

AB - Purpose: Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor α gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMDa) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men. Methods: Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40-79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression. Results: 2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p = 0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p = 0.004) lower total hip BMDa, a 0.12 SD (95%CI 0.02, 0.23; p = 0.026) lower lumbar spine BMDa and a 0.18 SD (95%CI 0.06, 0.29; p = 0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness. Conclusions: Our data replicate previous associations found between SNPs in the 6q25 locus and BMDa at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD. © 2011 Holliday et al.

U2 - 10.1371/journal.pone.0022037

DO - 10.1371/journal.pone.0022037

M3 - Article

C2 - 21760950

VL - 6

JO - PLoS ONE

JF - PLoS ONE

IS - 7

M1 - e22037

ER -

The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men

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