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, G. Bártfai, Felipe Casanueva, Joseph D. Finn, Gianni Forti, Aleksander Giwercman, Thang S. Han, Krzysztof Kula, Fernand Labrie, Michael E J Lean, Neil Pendleton & 4 others Margus Punab, Frederick C W Wu, Terence W. O'Neill, EMAS study group the EMAS study group

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Article numbere22037
JournalPLoS One
Volume6
Issue number7
DOIs
Publication statusPublished - 2011

Fingerprint

radius (bone)
bone density
Bone Density
Single Nucleotide Polymorphism
Minerals
Bone
Ultrasonics
bones
Bone Remodeling
loci
hips
lumbar spine
Hip
computed tomography
single nucleotide polymorphism
Polymorphism
Spine
Tomography
Nucleotides
Bone and Bones

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Holliday, K. L., Pye, S. R., Thomson, W., Boonen, S., Borghs, H., Vanderschueren, D., ... the EMAS study group, EMAS. S. G. (2011). The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men. PLoS One, 6(7), [e22037]. https://doi.org/10.1371/journal.pone.0022037

The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men. / Holliday, Kate L.; Pye, Stephen R.; Thomson, Wendy; Boonen, Steven; Borghs, Herman; Vanderschueren, Dirk; Gielen, Evelien; Huhtaniemi, Ilpo T.; Adams, Judith E.; Ward, Kate A.; Bártfai, G.; Casanueva, Felipe; Finn, Joseph D.; Forti, Gianni; Giwercman, Aleksander; Han, Thang S.; Kula, Krzysztof; Labrie, Fernand; Lean, Michael E J; Pendleton, Neil; Punab, Margus; Wu, Frederick C W; O'Neill, Terence W.; the EMAS study group, EMAS study group.

In: PLoS One, Vol. 6, No. 7, e22037, 2011.

Research output: Contribution to journalArticle

Holliday, KL, Pye, SR, Thomson, W, Boonen, S, Borghs, H, Vanderschueren, D, Gielen, E, Huhtaniemi, IT, Adams, JE, Ward, KA, Bártfai, 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 & the EMAS study group, EMASSG 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
Holliday, Kate L. ; Pye, Stephen R. ; Thomson, Wendy ; Boonen, Steven ; Borghs, Herman ; Vanderschueren, Dirk ; Gielen, Evelien ; Huhtaniemi, Ilpo T. ; Adams, Judith E. ; Ward, Kate A. ; Bártfai, G. ; Casanueva, Felipe ; Finn, Joseph D. ; Forti, Gianni ; Giwercman, Aleksander ; Han, Thang S. ; Kula, Krzysztof ; Labrie, Fernand ; Lean, Michael E J ; Pendleton, Neil ; Punab, Margus ; Wu, Frederick C W ; O'Neill, Terence W. ; the EMAS study group, EMAS study group. / The ESR1 (6q25) locus is associated with calcaneal ultrasound parameters and radial volumetric bone mineral density in European men. In: PLoS One. 2011 ; Vol. 6, No. 7.
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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.",
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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 - Bártfai, G.

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 - the EMAS study group, 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.

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.

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