Genetic analysis of vertebral trabecular bone density and cross-sectional area in older men

J. M. Zmuda; L. M. Yerges-Armstrong; S. P. Moffett; L. Klei; C. M. Kammerer; K. Roeder; J. A. Cauley; A. Kuipers; K. E. Ensrud; C. S. Nestlerode; A. R. Hoffman; C. E. Lewis; T. F. Lang; E. Barrett-Connor; R. E. Ferrell; E. S. Orwoll

doi:10.1007/s00198-010-1296-0

Genetic analysis of vertebral trabecular bone density and cross-sectional area in older men

J. M. Zmuda, L. M. Yerges-Armstrong, S. P. Moffett, L. Klei, C. M. Kammerer, K. Roeder, J. A. Cauley, A. Kuipers, K. E. Ensrud, C. S. Nestlerode, A. R. Hoffman, C. E. Lewis, T. F. Lang, E. Barrett-Connor, R. E. Ferrell, E. S. Orwoll

Medicine - Veteran's Administration Medical Center

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

23 Scopus citations

Abstract

Summary: We investigated 383 bone candidate genes for associations between single nucleotide polymorphisms and vertebral trabecular volumetric bone mineral density (vBMD) and cross-sectional area (CSA) in 2,018 Caucasian men aged ≥65 years. SNPs in TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE were associated with vBMD and SNPs in CYP11B1, DVL2, DLX5, WNT4, and PAX7 were associated with CSA in independent study samples (p<0.005). Inroduction: Vertebral bone mineral density and cross-sectional area are important determinants of vertebral bone strength. Little is known about the specific genetic variants that influence these phenotypes in humans. Methods: We investigated the potential genetic variants associated with vertebral trabecular volumetric BMD and CSA measured by quantitative computed tomography. We initially tested for association between these phenotypes and 4608 tagging and potentially functional single nucleotide polymorphisms (SNPs) in 383 candidate genes in 862 community-dwelling Caucasian men aged ≥65 years in the Osteoporotic Fractures in Men Study. Results: SNP associations were then validated by genotyping an additional 1,156 randomly sampled men from the same cohort. We identified 11 SNPs in 10 genes (TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE) that were consistently associated with trabecular vBMD and five SNPs in five genes (CYP11B1, DVL2, DLX5, WNT4, and PAX7) that were consistently associated with CSA in both samples (p<0.005). Conclusion: None of the SNPs associated with trabecular vBMD were associated with CSA. Our findings raise the possibility that at least some of the loci for vertebral trabecular BMD and bone size may be distinct.

Original language	English (US)
Pages (from-to)	1079-1090
Number of pages	12
Journal	Osteoporosis International
Volume	22
Issue number	4
DOIs	https://doi.org/10.1007/s00198-010-1296-0
State	Published - Apr 2011

Bibliographical note

Funding Information:
Genotyping was supported by grant R01-AR051124 from The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140. Laura Yerges was supported as a pre-doctoral fellow on National Institute on Aging T32-AG000181-16. This publication was also made possible by grant number UL1-RR024153 from the National Center for Research Resources (NCRR), a component of the NIH and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.

Keywords

BMD
Genetics
Men
Osteoporosis
Polymorphism
QCT

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10.1007/s00198-010-1296-0

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Zmuda, J. M., Yerges-Armstrong, L. M., Moffett, S. P., Klei, L., Kammerer, C. M., Roeder, K., Cauley, J. A., Kuipers, A., Ensrud, K. E., Nestlerode, C. S., Hoffman, A. R., Lewis, C. E., Lang, T. F., Barrett-Connor, E., Ferrell, R. E., & Orwoll, E. S. (2011). Genetic analysis of vertebral trabecular bone density and cross-sectional area in older men. Osteoporosis International, 22(4), 1079-1090. https://doi.org/10.1007/s00198-010-1296-0

Zmuda, JM, Yerges-Armstrong, LM, Moffett, SP, Klei, L, Kammerer, CM, Roeder, K, Cauley, JA, Kuipers, A, Ensrud, KE, Nestlerode, CS, Hoffman, AR, Lewis, CE, Lang, TF, Barrett-Connor, E, Ferrell, RE & Orwoll, ES 2011, 'Genetic analysis of vertebral trabecular bone density and cross-sectional area in older men', Osteoporosis International, vol. 22, no. 4, pp. 1079-1090. https://doi.org/10.1007/s00198-010-1296-0

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abstract = "Summary: We investigated 383 bone candidate genes for associations between single nucleotide polymorphisms and vertebral trabecular volumetric bone mineral density (vBMD) and cross-sectional area (CSA) in 2,018 Caucasian men aged ≥65 years. SNPs in TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE were associated with vBMD and SNPs in CYP11B1, DVL2, DLX5, WNT4, and PAX7 were associated with CSA in independent study samples (p<0.005). Inroduction: Vertebral bone mineral density and cross-sectional area are important determinants of vertebral bone strength. Little is known about the specific genetic variants that influence these phenotypes in humans. Methods: We investigated the potential genetic variants associated with vertebral trabecular volumetric BMD and CSA measured by quantitative computed tomography. We initially tested for association between these phenotypes and 4608 tagging and potentially functional single nucleotide polymorphisms (SNPs) in 383 candidate genes in 862 community-dwelling Caucasian men aged ≥65 years in the Osteoporotic Fractures in Men Study. Results: SNP associations were then validated by genotyping an additional 1,156 randomly sampled men from the same cohort. We identified 11 SNPs in 10 genes (TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE) that were consistently associated with trabecular vBMD and five SNPs in five genes (CYP11B1, DVL2, DLX5, WNT4, and PAX7) that were consistently associated with CSA in both samples (p<0.005). Conclusion: None of the SNPs associated with trabecular vBMD were associated with CSA. Our findings raise the possibility that at least some of the loci for vertebral trabecular BMD and bone size may be distinct.",

keywords = "BMD, Genetics, Men, Osteoporosis, Polymorphism, QCT",

author = "Zmuda, {J. M.} and Yerges-Armstrong, {L. M.} and Moffett, {S. P.} and L. Klei and Kammerer, {C. M.} and K. Roeder and Cauley, {J. A.} and A. Kuipers and Ensrud, {K. E.} and Nestlerode, {C. S.} and Hoffman, {A. R.} and Lewis, {C. E.} and Lang, {T. F.} and E. Barrett-Connor and Ferrell, {R. E.} and Orwoll, {E. S.}",

note = "Funding Information: Genotyping was supported by grant R01-AR051124 from The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140. Laura Yerges was supported as a pre-doctoral fellow on National Institute on Aging T32-AG000181-16. This publication was also made possible by grant number UL1-RR024153 from the National Center for Research Resources (NCRR), a component of the NIH and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. ",

year = "2011",

month = apr,

doi = "10.1007/s00198-010-1296-0",

language = "English (US)",

volume = "22",

pages = "1079--1090",

journal = "Osteoporosis International",

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TY - JOUR

T1 - Genetic analysis of vertebral trabecular bone density and cross-sectional area in older men

AU - Zmuda, J. M.

AU - Yerges-Armstrong, L. M.

AU - Moffett, S. P.

AU - Klei, L.

AU - Kammerer, C. M.

AU - Roeder, K.

AU - Cauley, J. A.

AU - Kuipers, A.

AU - Ensrud, K. E.

AU - Nestlerode, C. S.

AU - Hoffman, A. R.

AU - Lewis, C. E.

AU - Lang, T. F.

AU - Barrett-Connor, E.

AU - Ferrell, R. E.

AU - Orwoll, E. S.

N1 - Funding Information: Genotyping was supported by grant R01-AR051124 from The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140. Laura Yerges was supported as a pre-doctoral fellow on National Institute on Aging T32-AG000181-16. This publication was also made possible by grant number UL1-RR024153 from the National Center for Research Resources (NCRR), a component of the NIH and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.

PY - 2011/4

Y1 - 2011/4

N2 - Summary: We investigated 383 bone candidate genes for associations between single nucleotide polymorphisms and vertebral trabecular volumetric bone mineral density (vBMD) and cross-sectional area (CSA) in 2,018 Caucasian men aged ≥65 years. SNPs in TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE were associated with vBMD and SNPs in CYP11B1, DVL2, DLX5, WNT4, and PAX7 were associated with CSA in independent study samples (p<0.005). Inroduction: Vertebral bone mineral density and cross-sectional area are important determinants of vertebral bone strength. Little is known about the specific genetic variants that influence these phenotypes in humans. Methods: We investigated the potential genetic variants associated with vertebral trabecular volumetric BMD and CSA measured by quantitative computed tomography. We initially tested for association between these phenotypes and 4608 tagging and potentially functional single nucleotide polymorphisms (SNPs) in 383 candidate genes in 862 community-dwelling Caucasian men aged ≥65 years in the Osteoporotic Fractures in Men Study. Results: SNP associations were then validated by genotyping an additional 1,156 randomly sampled men from the same cohort. We identified 11 SNPs in 10 genes (TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE) that were consistently associated with trabecular vBMD and five SNPs in five genes (CYP11B1, DVL2, DLX5, WNT4, and PAX7) that were consistently associated with CSA in both samples (p<0.005). Conclusion: None of the SNPs associated with trabecular vBMD were associated with CSA. Our findings raise the possibility that at least some of the loci for vertebral trabecular BMD and bone size may be distinct.

AB - Summary: We investigated 383 bone candidate genes for associations between single nucleotide polymorphisms and vertebral trabecular volumetric bone mineral density (vBMD) and cross-sectional area (CSA) in 2,018 Caucasian men aged ≥65 years. SNPs in TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE were associated with vBMD and SNPs in CYP11B1, DVL2, DLX5, WNT4, and PAX7 were associated with CSA in independent study samples (p<0.005). Inroduction: Vertebral bone mineral density and cross-sectional area are important determinants of vertebral bone strength. Little is known about the specific genetic variants that influence these phenotypes in humans. Methods: We investigated the potential genetic variants associated with vertebral trabecular volumetric BMD and CSA measured by quantitative computed tomography. We initially tested for association between these phenotypes and 4608 tagging and potentially functional single nucleotide polymorphisms (SNPs) in 383 candidate genes in 862 community-dwelling Caucasian men aged ≥65 years in the Osteoporotic Fractures in Men Study. Results: SNP associations were then validated by genotyping an additional 1,156 randomly sampled men from the same cohort. We identified 11 SNPs in 10 genes (TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE) that were consistently associated with trabecular vBMD and five SNPs in five genes (CYP11B1, DVL2, DLX5, WNT4, and PAX7) that were consistently associated with CSA in both samples (p<0.005). Conclusion: None of the SNPs associated with trabecular vBMD were associated with CSA. Our findings raise the possibility that at least some of the loci for vertebral trabecular BMD and bone size may be distinct.

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KW - Genetics

KW - Men

KW - Osteoporosis

KW - Polymorphism

KW - QCT

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Genetic analysis of vertebral trabecular bone density and cross-sectional area in older men

Abstract

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